Streptococcus pneumoniae Polynucleotides and Sequences

ABSTRACT

The present invention provides polynucleotide sequences of the genome of  Streptococcus pneumoniae , polypeptide sequences encoded by the polynucleotide sequences, corresponding polynucleotides and polypeptides, vectors and hosts comprising the polynucleotides, and assays and other uses thereof. The present invention further provides polynucleotide and polypeptide sequence information stored on computer readable media, and computer-based systems and methods which facilitate its use.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 10/158,844, filed Jun. 3, 2002, which is a divisional of U.S. application Ser. No. 08/961,527, filed Oct. 30, 1997, which is a nonprovisional of and claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 60/029,960, filed Oct. 31, 1996, each of which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to the field of molecular biology. In particular, it relates to, among other things, nucleotide sequences of Streptococcus pneumoniae, contigs, ORFs, fragments, probes, primers and related polynucleotides thereof, peptides and polypeptides encoded by the sequences, and uses of the polynucleotides and sequences thereof, such as in fermentation, polypeptide production, assays and pharmaceutical development, among others.

BACKGROUND OF THE INVENTION

Streptococcus pneumoniae has been one of the most extensively studied microorganisms since its first isolation in 1881. It was the object of many investigations that led to important scientific discoveries. In 1928, Griffith observed that when heat-killed encapsulated pneumococci and live strains constitutively lacking any capsule were concomitantly injected into mice, the nonencapsulated could be converted into encapsulated pneumococci with the same capsular type as the heat-killed strain. Years later, the nature of this “transforming principle,” or carrier of genetic information, was shown to be DNA. (Avery, O. T., et al., J. Exp. Med., 79:137-157 (1944)).

In spite of the vast number of publications on S. pneumoniae many questions about its virulence are still unanswered, and this pathogen remains a major causative agent of serious human disease, especially community-acquired pneumonia. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991)). In addition, in developing countries, the pneumococcus is responsible for the death of a large number of children under the age of 5 years from pneumococcal pneumonia. The incidence of pneumococcal disease is highest in infants under 2 years of age and in people over 60 years of age. Pneumococci are the second most frequent cause (after Haemophilus influenzae type b) of bacterial meningitis and otitis media in children. With the recent introduction of conjugate vaccines for H. influenzae type b, pneumococcal meningitis is likely to become increasingly prominent. S. pneumoniae is the most important etiologic agent of community-acquired pneumonia in adults and is the second most common cause of bacterial meningitis behind Neisseria meningitidis.

The antibiotic generally prescribed to treat S. pneumoniae is benzylpenicillin, although resistance to this and to other antibiotics is found occasionally. Pneumococcal resistance to penicillin results from mutations in its penicillin-binding proteins. In uncomplicated pneumococcal pneumonia caused by a sensitive strain, treatment with penicillin is usually successful unless started too late. Erythromycin or clindamycin can be used to treat pneumonia in patients hypersensitive to penicillin, but resistant strains to these drugs exist. Broad spectrum antibiotics (e.g., the tetracyclines) may also be effective, although tetracycline-resistant strains are not rare. In spite of the availability of antibiotics, the mortality of pneumococcal bacteremia in the last four decades has remained stable between 25 and 29%. (Gillespie, S. H., et al., J. Med. Microbiol. 28:237-248 (1989).

S. pneumoniae is carried in the upper respiratory tract by many healthy individuals. It has been suggested that attachment of pneumococci is mediated by a disaccharide receptor on fibronectin, present on human pharyngeal epithelial cells. (Anderson, B. J., et al., J. Immunol. 142:2464-2468 (1989). The mechanisms by which pneumococci translocate from the nasopharynx to the lung, thereby causing pneumonia, or migrate to the blood, giving rise to bacteremia or septicemia, are poorly understood. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991).

Various proteins have been suggested to be involved in the pathogenicity of S. pneumoniae, however, only a few of them have actually been confirmed as virulence factors. Pneumococci produce an IgA1 protease that might interfere with host defense at mucosal surfaces. (Kornfield, S. J., et al., Rev. Inf. Dis. 3:521-534 (1981). S. pneumoniae also produces neuraminidase, an enzyme that may facilitate attachment to epithelial cells by cleaving sialic acid from the host glycolipids and gangliosides. Partially purified neuraminidase was observed to induce meningitis-like symptoms in mice; however, the reliability of this finding has been questioned because the neuraminidase preparations used were probably contaminated with cell wall products. Other pneumococcal proteins besides neuraminidase are involved in the adhesion of pneumococci to epithelial and endothelial cells. These pneumococcal proteins have as yet not been identified. Recently, Cundell et al., reported that peptide permeases can modulate pneumococcal adherence to epithelial and endothelial cells. It was, however, unclear whether these permeases function directly as adhesions or whether they enhance adherence by modulating the expression of pneumococcal adhesions. (DeVelasco, E. A., et al., Micro. Rev. 59:591-603 (1995). A better understanding of the virulence factors determining its pathogenicity will need to be developed to cope with the devastating effects of pneumococcal disease in humans.

Ironically, despite the prominent role of S. pneumoniae in the discovery of DNA, little is known about the molecular genetics of the organism. The S. pneumoniae genome consists of one circular, covalently closed, double-stranded DNA and a collection of so-called variable accessory elements, such as prophages, plasmids, transposons and the like. Most physical characteristics and almost all of the genes of S. pneumoniae are unknown. Among the few that have been identified, most have not been physically mapped or characterized in detail. Only a few genes of this organism have been sequenced. (See, for instance current versions of GENBANK and other nucleic acid databases, and references that relate to the genome of S. pneumoniae such as those set out elsewhere herein.)

It is clear that the etiology of diseases mediated or exacerbated by S. pneumoniae, infection involves the programmed expression of S. pneumoniae genes, and that characterizing the genes and their patterns of expression would add dramatically to our understanding of the organism and its host interactions. Knowledge of S. pneumoniae genes and genomic organization would improve our understanding of disease etiology and lead to improved and new ways of preventing, ameliorating, arresting and reversing diseases. Moreover, characterized genes and genomic fragments of S. pneumoniae would provide reagents for, among other things, detecting, characterizing and controlling S. pneumoniae infections. There is a need to characterize the genome of S. pneumoniae and for polynucleotides of this organism.

SUMMARY OF THE INVENTION

The present invention is based on the sequencing of fragments of the Streptococcus pneumoniae genome. The primary nucleotide sequences which were generated are provided in SEQ ID NOS:1-391.

The present invention provides the nucleotide sequence of several hundred contigs of the Streptococcus pneumoniae genome, which are listed in tables below and set out in the Sequence Listing submitted herewith, and representative fragments thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan. In one embodiment, the present invention is provided as contiguous strings of primary sequence information corresponding to the nucleotide sequences depicted in SEQ ID NOS:1-391.

The present invention further provides nucleotide sequences which are at least 95% identical to the nucleotide sequences of SEQ ID NOS:1-391.

The nucleotide sequence of SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NOS:1-391 may be provided in a variety of mediums to facilitate its use. In one application of this embodiment, the sequences of the present invention are recorded on computer readable media. Such media includes, but is not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

The present invention further provides systems, particularly computer-based systems which contain the sequence information herein described stored in a data storage means. Such systems are designed to identify commercially important fragments of the Streptococcus pneumoniae genome.

Another embodiment of the present invention is directed to fragments of the Streptococcus pneumoniae genome having particular structural or functional attributes. Such fragments of the Streptococcus pneumoniae genome of the present invention include, but are not limited to, fragments which encode peptides, hereinafter referred to as open reading frames or ORFs, fragments which modulate the expression of an operably linked ORF, hereinafter referred to as expression modulating fragments or EMFs, and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in a sample, hereinafter referred to as diagnostic fragments or DFs.

Each of the ORFs in fragments of the Streptococcus pneumoniae genome disclosed in Tables 1-3, and the EMFs found 5′ to the ORFs, can be used in numerous ways as polynucleotide reagents. For instance, the sequences can be used as diagnostic probes or amplification primers for detecting or determining the presence of a specific microbe in a sample, to selectively control gene expression in a host and in the production of polypeptides, such as polypeptides encoded by ORFs of the present invention, particular those polypeptides that have a pharmacological activity.

The present invention further includes recombinant constructs comprising one or more fragments of the Streptococcus pneumoniae genome of the present invention. The recombinant constructs of the present invention comprise vectors, such as a plasmid or viral vector, into which a fragment of the Streptococcus pneumoniae has been inserted.

The present invention further provides host cells containing any of the isolated fragments of the Streptococcus pneumoniae genome of the present invention. The host cells can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic cell, such as a yeast cell, or a procaryotic cell such as a bacterial cell.

The present invention is further directed to isolated polypeptides and proteins encoded by ORFs of the present invention. A variety of methods, well known to those of skill in the art, routinely may be utilized to obtain any of the polypeptides and proteins of the present invention. For instance, polypeptides and proteins of the present invention having relatively short, simple amino acid sequences readily can be synthesized using commercially available automated peptide synthesizers. Polypeptides and proteins of the present invention also may be purified from bacterial cells which naturally produce the protein. Yet another alternative is to purify polypeptide and proteins of the present invention from cells which have been altered to express them.

The invention further provides methods of obtaining homologs of the fragments of the Streptococcus pneumoniae genome of the present invention and homologs of the proteins encoded by the ORFs of the present invention. Specifically, by using the nucleotide and amino acid sequences disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.

The invention further provides antibodies which selectively bind polypeptides and proteins of the present invention. Such antibodies include both monoclonal and polyclonal antibodies.

The invention further provides hybridomas which produce the above-described antibodies. A hybridoma is an immortalized cell line which is capable of secreting a specific monoclonal antibody.

The present invention further provides methods of identifying test samples derived from cells which express one of the ORFs of the present invention, or a homolog thereof. Such methods comprise incubating a test sample with one or more of the antibodies of the present invention, or one or more of the DFs of the present invention, under conditions which allow a skilled artisan to determine if the sample contains the ORF or product produced therefrom.

In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the above-described assays.

Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the antibodies, or one of the DFs of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of bound antibodies or hybridized DFs.

Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents capable of binding to a polypeptide or protein encoded by one of the ORFs of the present invention. Specifically, such agents include, as further described below, antibodies, peptides, carbohydrates, pharmaceutical agents and the like. Such methods comprise steps of: (a) contacting an agent with an isolated protein encoded by one of the ORFs of the present invention; and (b) determining whether the agent binds to said protein.

The present genomic sequences of Streptococcus pneumoniae will be of great value to all laboratories working with this organism and for a variety of commercial purposes. Many fragments of the Streptococcus pneumoniae genome will be immediately identified by similarity searches against GenBank or protein databases and will be of immediate value to Streptococcus pneumoniae researchers and for immediate commercial value for the production of proteins or to control gene expression.

The methodology and technology for elucidating extensive genomic sequences of bacterial and other genomes has and will greatly enhance the ability to analyze and understand chromosomal organization. In particular, sequenced contigs and genomes will provide the models for developing tools for the analysis of chromosome structure and function, including the ability to identify genes within large segments of genomic DNA, the structure, position, and spacing of regulatory elements, the identification of genes with potential industrial applications, and the ability to do comparative genomic and molecular phylogeny.

DESCRIPTION OF THE FIGURES

FIG. 1 is a block diagram of a computer system (102) that can be used to implement computer-based systems of present invention.

FIG. 2 is a schematic diagram depicting the data flow and computer programs used to collect, assemble, edit and annotate the contigs of the Streptococcus pneumoniae genome of the present invention. Both Macintosh and Unix platforms are used to handle the AB 373 and 377 sequence data files, largely as described in Kerlavage et al., Proceedings of the Twenty-Sixth Annual Hawaii International Conference on System Sciences, 585, IEEE Computer Society Press, Washington D.C. (1993). Factura (AB) is a Macintosh program designed for automatic vector sequence removal and end-trimming of sequence files. The program Loadis runs on a Macintosh platform and parses the feature data extracted from the sequence files by Factura to the Unix based Streptococcus pneumoniae relational database. Assembly of contigs (and whole genome sequences) is accomplished by retrieving a specific set of sequence files and their associated features using Extrseq, a Unix utility for retrieving sequences from an SQL database. The resulting sequence file is processed by seq_filter to trim portions of the sequences with more than 2% ambiguous nucleotides. The sequence files were assembled using TIGR Assembler, an assembly engine designed at The Institute for Genomic Research (TIGR) for rapid and accurate assembly of thousands of sequence fragments. The collection of contigs generated by the assembly step is loaded into the database with the lassie program. Identification of open reading frames (ORFs) is accomplished by processing contigs with zorf or GenMark. The ORFs are searched against S. pneumoniae sequences from GenBank and against all protein sequences using the BLASTN and BLASTP programs, described in Altschul et al., J. Mol. Biol. 215: 403-410 (1990)). Results of the ORF determination and similarity searching steps were loaded into the database. As described below, some results of the determination and the searches are set out in Tables 1-3.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is based on the sequencing of fragments of the Streptococcus pneumoniae genome and analysis of the sequences. The primary nucleotide sequences generated by sequencing the fragments are provided in SEQ ID NOS:1-391. (As used herein, the “primary sequence” refers to the nucleotide sequence represented by the IUPAC nomenclature system.)

In addition to the aforementioned Streptococcus pneumoniae polynucleotide and polynucleotide sequences, the present invention provides the nucleotide sequences of SEQ ID NOS:1-391, or representative fragments thereof, in a form which can be readily used, analyzed, and interpreted by a skilled artisan.

As used herein, a “representative fragment of the nucleotide sequence depicted in SEQ ID NOS:1-391” refers to any portion of the SEQ ID NOS:1-391 which is not presently represented within a publicly available database. Preferred representative fragments of the present invention are Streptococcus pneumoniae open reading frames (ORFs), expression modulating fragment (EMFs) and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in sample (DFs). A non-limiting identification of preferred representative fragments is provided in Tables 1-3. As discussed in detail below, the information provided in SEQ ID NOS:1-391 and in Tables 1-3 together with routine cloning, synthesis, sequencing and assay methods will enable those skilled in the art to clone and sequence all “representative fragments” of interest, including open reading frames encoding a large variety of Streptococcus pneumoniae proteins.

While the presently disclosed sequences of SEQ ID NOS:1-391 are highly accurate, sequencing techniques are not perfect and, in relatively rare instances, further investigation of a fragment or sequence of the invention may reveal a nucleotide sequence error present in a nucleotide sequence disclosed in SEQ ID NOS:1-391. However, once the present invention is made available (i.e., once the information in SEQ ID NOS:1-391 and Tables 1-3 has been made available), resolving a rare sequencing error in SEQ ID NOS:1-391 will be well within the skill of the art. The present disclosure makes available sufficient sequence information to allow any of the described contigs or portions thereof to be obtained readily by straightforward application of routine techniques. Further sequencing of such polynucleotide may proceed in like manner using manual and automated sequencing methods which are employed ubiquitous in the art. Nucleotide sequence editing software is publicly available. For example, Applied Biosystem's (AB) AutoAssembler can be used as an aid during visual inspection of nucleotide sequences. By employing such routine techniques potential errors readily may be identified and the correct sequence then may be ascertained by targeting further sequencing effort, also of a routine nature, to the region containing the potential error.

Even if all of the very rare sequencing errors in SEQ ID NOS:1-391 were corrected, the resulting nucleotide sequences would still be at least 95% identical, nearly all would be at least 99% identical, and the great majority would be at least 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391.

As discussed elsewhere herein, polynucleotides of the present invention readily may be obtained by routine application of well known and standard procedures for cloning and sequencing DNA. Detailed methods for obtaining libraries and for sequencing are provided below, for instance. A wide variety of Streptococcus pneumoniae strains that can be used to prepare S. pneumoniae genomic DNA for cloning and for obtaining polynucleotides of the present invention are available to the public from recognized depository institutions, such as the American Type Culture Collection (ATCC). While the present invention is enabled by the sequences and other information herein disclosed, the S. pneumoniae strain that provided the DNA of the present Sequence Listing, Strain 7/87 14.8.91, has been deposited in the ATCC, as a convenience to those of skill in the art. As a further convenience, a library of S. pneumoniae genomic DNA, derived from the same strain, also has been deposited in the ATCC. The S. pneumoniae strain was deposited on Oct. 10, 1996, and was given Deposit No. 55840, and the cDNA library was deposited on Oct. 11, 1996 and was given Deposit No. 97755. The genomic fragments in the library are 15 to 20 kb fragments generated by partial Sau3A1 digestion and they are inserted into the BamHI site in the well-known lambda-derived vector lambda DASH II (Stratagene, La Jolla, Calif.). The provision of the deposits is not a waiver of any rights of the inventors or their assignees in the present subject matter.

The nucleotide sequences of the genomes from different strains of Streptococcus pneumoniae differ somewhat. However, the nucleotide sequences of the genomes of all Streptococcus pneumoniae strains will be at least 95% identical, in corresponding part, to the nucleotide sequences provided in SEQ ID NOS:1-391. Nearly all will be at least 99% identical and the great majority will be 99.9% identical.

Thus, the present invention further provides nucleotide sequences which are at least 95%, preferably 99% and most preferably 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391, in a form which can be readily used, analyzed and interpreted by the skilled artisan.

Methods for determining whether a nucleotide sequence is at least 95%, at least 99% or at least 99.9% identical to the nucleotide sequences of SEQ ID NOS:1-391 are routine and readily available to the skilled artisan. For example, the well known fasta algorithm described in Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85: 2444 (1988) can be used to generate the percent identity of nucleotide sequences. The BLASTN program also can be used to generate an identity score of polynucleotides compared to one another.

Computer Related Embodiments

The nucleotide sequences provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a polynucleotide sequence of SEQ ID NOS:1-391 may be “provided” in a variety of mediums to facilitate use thereof. As used herein, provided refers to a manufacture, other than an isolated nucleic acid molecule, which contains a nucleotide sequence of the present invention; i.e., a nucleotide sequence provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a polynucleotide of SEQ ID NOS:1-391. Such a manufacture provides a large portion of the Streptococcus pneumoniae genome and parts thereof (e.g., a Streptococcus pneumoniae open reading frame (ORF)) in a form which allows a skilled artisan to examine the manufacture using means not directly applicable to examining the Streptococcus pneumoniae genome or a subset thereof as it exists in nature or in purified form.

In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, “computer readable media” refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories, such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the present invention. Likewise, it will be clear to those of skill how additional computer readable media that may be developed also can be used to create analogous manufactures having recorded thereon a nucleotide sequence of the present invention.

As used herein, “recorded” refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently know methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information of the present invention.

A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and MicroSoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data-processor structuring formats (e.g., text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention.

Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. Thus, by providing in computer readable form the nucleotide sequences of SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most preferably at least 99.9% identical to a sequence of SEQ ID NOS:1-391 the present invention enables the skilled artisan routinely to access the provided sequence information for a wide variety of purposes.

The examples which follow demonstrate how software which implements the BLAST (Altschul et al., J. Mol. Biol. 215:403-410 (1990)) and BLAZE (Brutlag et al., Comp. Chem. 17:203-207 (1993)) search algorithms on a Sybase system was used to identify open reading frames (ORFs) within the Streptococcus pneumoniae genome which contain homology to ORFs or proteins from both Streptococcus pneumoniae and from other organisms. Among the ORFs discussed herein are protein encoding fragments of the Streptococcus pneumoniae genome useful in producing commercially important proteins, such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.

The present invention further provides systems, particularly computer-based systems, which contain the sequence information described herein. Such systems are designed to identify, among other things, commercially important fragments of the Streptococcus pneumoniae genome.

As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based systems are suitable for use in the present invention.

As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means.

As used herein, “data storage means” refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.

As used herein, “search means” refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of the present genomic sequences which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. Examples of such software includes, but is not limited to, MacPattern (EMBL), BLASTN and BLASTX (NCBIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems.

As used herein, a “target sequence” can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length.

As used herein, “a target structural motif,” or “target motif,” refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzymic active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).

A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. A preferred format for an output means ranks fragments of the Streptococcus pneumoniae genomic sequences possessing varying degrees of homology to the target sequence or target motif. Such presentation provides a skilled artisan with a ranking of sequences which contain various amounts of the target sequence or target motif and identifies the degree of homology contained in the identified fragment.

A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the Streptococcus pneumoniae genome. In the present examples, implementing software which implement the BLAST and BLAZE algorithms, described in Altschul et al., J. Mol. Biol. 215: 403-410 (1990), is used to identify open reading frames within the Streptococcus pneumoniae genome. A skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer-based systems of the present invention. Of course, suitable proprietary systems that may be known to those of skill also may be employed in this regard.

FIG. 1 provides a block diagram of a computer system illustrative of embodiments of this aspect of present invention. The computer system 102 includes a processor 106 connected to a bus 104. Also connected to the bus 104 are a main memory 108 (preferably implemented as random access memory, RAM) and a variety of secondary storage devices 110, such as a hard drive 112 and a removable medium storage device 114. The removable medium storage device 114 may represent, for example, a floppy disk drive, a CD-ROM drive, a magnetic tape drive, etc. A removable storage medium 116 (such as a floppy disk, a compact disk, a magnetic tape, etc.) containing control logic and/or data recorded therein may be inserted into the removable medium storage device 114. The computer system 102 includes appropriate software for reading the control logic and/or the data from the removable medium storage device 114, once it is inserted into the removable medium storage device 114.

A nucleotide sequence of the present invention may be stored in a well known manner in the main memory 108, any of the secondary storage devices 110, and/or a removable storage medium 116. During execution, software for accessing and processing the genomic sequence (such as search tools, comparing tools, etc.) reside in main memory 108, in accordance with the requirements and operating parameters of the operating system, the hardware system and the software program or programs.

Biochemical Embodiments

Other embodiments of the present invention are directed to isolated fragments of the Streptococcus pneumoniae genome. The fragments of the Streptococcus pneumoniae genome of the present invention include, but are not limited to fragments which encode peptides and polypeptides, hereinafter open reading frames (ORFs), fragments which modulate the expression of an operably linked ORF, hereinafter expression modulating fragments (EMFs) and fragments which can be used to diagnose the presence of Streptococcus pneumoniae in a sample, hereinafter diagnostic fragments (DFs).

As used herein, an “isolated nucleic acid molecule” or an “isolated fragment of the Streptococcus pneumoniae genome” refers to a nucleic acid molecule possessing a specific nucleotide sequence which has been subjected to purification means to reduce, from the composition, the number of compounds which are normally associated with the composition. Particularly, the term refers to the nucleic acid molecules having the sequences set out in SEQ ID NOS:1-391, to representative fragments thereof as described above, to polynucleotides at least 95%, preferably at least 99% and especially preferably at least 99.9% identical in sequence thereto, also as set out above.

A variety of purification means can be used to generate the isolated fragments of the present invention. These include, but are not limited to methods which separate constituents of a solution based on charge, solubility, or size.

In one embodiment, Streptococcus pneumoniae DNA can be enzymatically sheared to produce fragments of 15-20 kb in length. These fragments can then be used to generate a Streptococcus pneumoniae library by inserting them into lambda clones as described in the Examples below. Primers flanking, for example, an ORF, such as those enumerated in Tables 1-3 can then be generated using nucleotide sequence information provided in SEQ ID NOS:1-391. Well known and routine techniques of PCR cloning then can be used to isolate the ORF from the lambda DNA library or Streptococcus pneumoniae genomic DNA. Thus, given the availability of SEQ ID NOS:1-391, the information in Tables 1, 2 and 3, and the information that may be obtained readily by analysis of the sequences of SEQ ID NOS:1-391 using methods set out above, those of skill will be enabled by the present disclosure to isolate any ORF-containing or other nucleic acid fragment of the present invention.

The isolated nucleic acid molecules of the present invention include, but are not limited to single stranded and double stranded DNA, and single stranded RNA. As used herein, an “open reading frame,” ORF, means a series of triplets coding for amino acids without any termination codons and is a sequence translatable into protein.

Tables 1, 2, and 3 list ORFs in the Streptococcus pneumoniae genomic contigs of the present invention that were identified as putative coding regions by the GeneMark software using organism-specific second-order Markov probability transition matrices. It will be appreciated that other criteria can be used, in accordance with well known analytical methods, such as those discussed herein, to generate more inclusive, more restrictive, or more selective lists.

Table 1 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that over a continuous region of at least 50 bases are 95% or more identical (by BLAST analysis) to a nucleotide sequence available through GenBank in October, 1997.

Table 2 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that are not in Table 1 and match, with a BLASTP probability score of 0.01 or less, a polypeptide sequence available through GenBank in October, 1997.

Table 3 sets out ORFs in the Streptococcus pneumoniae contigs of the present invention that do not match significantly, by BLASTP analysis, a polypeptide sequence available through GenBank in October, 1997.

In each table, the first and second columns identify the ORF by, respectively, contig number and ORF number within the contig; the third column indicates the first nucleotide of the ORF (actually the first nucleotide of the stop codon immediately preceding the ORF), counting from the 5′ end of the contig strand; and the fourth column, “stop (nt)” indicates the last nucleotide of the stop codon defining the 3′end of the ORF.

In Tables 1 and 2, column five, lists the Reference for the closest matching sequence available through GenBank. These reference numbers are the databases entry numbers commonly used by those of skill in the art, who will be familiar with their denominators. Descriptions of the nomenclature are available from the National Center for Biotechnology Information. Column six in Tables 1 and 2 provides the gene name of the matching sequence; column seven provides the BLAST identity score and column eight the BLAST similarity score from the comparison of the ORF and the homologous gene; and column nine indicates the length in nucleotides of the highest scoring segment pair identified by the BLAST identity analysis.

Each ORF described in the tables is defined by “start (nt)” (5′) and “stop (nt)” (3′) nucleotide position numbers. These position numbers refer to the boundaries of each ORF and provide orientation with respect to whether the forward or reverse strand is the coding strand and which reading frame the coding sequence is contained. The “start” position is the first nucleotide of the triplet encoding a stop codon just 5′ to the ORF and the “stop” position is the last nucleotide of the triplet encoding the next in-frame stop codon (i.e., the stop codon at the 3′ end of the ORF). Those of ordinary skill in the art appreciate that preferred fragments within each ORF described in the table include fragments of each ORF which include the entire sequence from the delineated “start” and “stop” positions excepting the first and last three nucleotides since these encode stop codons. Thus, polynucleotides set out as ORFs in the tables but lacking the three (3) 5′ nucleotides and the three (3) 3′ nucleotides are encompassed by the present invention. Those of skill also appreciate that particularly preferred are fragments within each ORF that are polynucleotide fragments comprising polypeptide coding sequence. As defined herein, “coding sequence” includes the fragment within an ORF beginning at the first in-frame ATG (triplet encoding methionine) and ending with the last nucleotide prior to the triplet encoding the 3′ stop codon. Preferred are fragments comprising the entire coding sequence and fragments comprising the entire coding sequence, excepting the coding sequence for the N-terminal methionine. Those of skill appreciate that the N-terminal methionine is often removed during post-translational processing and that polynucleotides lacking the ATG can be used to facilitate production of N-terminal fusion proteins which may be beneficial in the production or use of genetically engineered proteins. Of course, due to the degeneracy of the genetic code many polynucleotides can encode a given polypeptide. Thus, the invention further includes polynucleotides comprising a nucleotide sequence encoding a polypeptide sequence itself encoded by the coding sequence within an ORF described in Tables 1-3 herein. Further, polynucleotides at least 95%, preferably at least 99% and especially preferably at least 99.9% identical in sequence to the foregoing polynucleotides, are contemplated by the present invention.

Polypeptides encoded by polynucleotides described above and elsewhere herein are also provided by the present invention as are polypeptide comprising a an amino acid sequence at least about 95%, preferably at least 97% and even more preferably 99% identical to the amino acid sequence of a polypeptide encoded by an ORF shown in Tables 1-3. These polypeptides may or may not comprise an N-terminal methionine.

The concepts of percent identity and percent similarity of two polypeptide sequences is well understood in the art. For example, two polypeptides 10 amino acids in length which differ at three amino acid positions (e.g., at positions 1, 3 and 5) are said to have a percent identity of 70%. However, the same two polypeptides would be deemed to have a percent similarity of 80% if, for example at position 5, the amino acids moieties, although not identical, were “similar” (i.e., possessed similar biochemical characteristics). Many programs for analysis of nucleotide or amino acid sequence similarity, such as fasta and BLAST specifically list percent identity of a matching region as an output parameter. Thus, for instance, Tables 1 and 2 herein enumerate the percent identity of the highest scoring segment pair in each ORF and its listed relative. Further details concerning the algorithms and criteria used for homology searches are provided below and are described in the pertinent literature highlighted by the citations provided below.

It will be appreciated that other criteria can be used to generate more inclusive and more exclusive listings of the types set out in the tables. As those of skill will appreciate, narrow and broad searches both are useful. Thus, a skilled artisan can readily identify ORFs in contigs of the Streptococcus pneumoniae genome other than those listed in Tables 1-3, such as ORFs which are overlapping or encoded by the opposite strand of an identified ORF in addition to those ascertainable using the computer-based systems of the present invention.

As used herein, an “expression modulating fragment,” EMF, means a series of nucleotide molecules which modulates the expression of an operably linked ORF or EMF.

As used herein, a sequence is said to “modulate the expression of an operably linked sequence” when the expression of the sequence is altered by the presence of the EMF. EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are fragments which induce the expression or an operably linked ORF in response to a specific regulatory factor or physiological event.

EMF sequences can be identified within the contigs of the Streptococcus pneumoniae genome by their proximity to the ORFs provided in Tables 1-3. An intergenic segment, or a fragment of the intergenic segment, from about 10 to 200 nucleotides in length, taken from any one of the ORFs of Tables 1-3 will modulate the expression of an operably linked ORF in a fashion similar to that found with the naturally linked ORF sequence. As used herein, an “intergenic segment” refers to fragments of the Streptococcus pneumoniae genome which are between two ORF(s) herein described. EMFs also can be identified using known EMFs as a target sequence or target motif in the computer-based systems of the present invention. Further, the two methods can be combined and used together.

The presence and activity of an EMF can be confirmed using an EMF trap vector. An EMF trap vector contains a cloning site linked to a marker sequence. A marker sequence encodes an identifiable phenotype, such as antibiotic resistance or a complementing nutrition auxotrophic factor, which can be identified or assayed when the EMF trap vector is placed within an appropriate host under appropriate conditions. As described above, a EMF will modulate the expression of an operably linked marker sequence. A more detailed discussion of various marker sequences is provided below. A sequence which is suspected as being an EMF is cloned in all three reading frames in one or more restriction sites upstream from the marker sequence in the EMF trap vector. The vector is then transformed into an appropriate host using known procedures and the phenotype of the transformed host in examined under appropriate conditions. As described above, an EMF will modulate the expression of an operably linked marker sequence.

As used herein, a “diagnostic fragment,” DF, means a series of nucleotide molecules which selectively hybridize to Streptococcus pneumoniae sequences. DFs can be readily identified by identifying unique sequences within contigs of the Streptococcus pneumoniae genome, such as by using well-known computer analysis software, and by generating and testing probes or amplification primers consisting of the DF sequence in an appropriate diagnostic format which determines amplification or hybridization selectivity.

The sequences falling within the scope of the present invention are not limited to the specific sequences herein described, but also include allelic and species variations thereof. Allelic and species variations can be routinely determined by comparing the sequences provided in SEQ ID NOS:1-391, a representative fragment thereof, or a nucleotide sequence at least 95%, preferably at least 99% and most at least preferably 99.9% identical to SEQ ID NOS:1-391, with a sequence from another isolate of the same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon for another which encodes the same amino acid is expressly contemplated. Any specific sequence disclosed herein can be readily screened for errors by resequencing a particular fragment, such as an ORF, in both directions (i.e., sequence both strands). Alternatively, error screening can be performed by sequencing corresponding polynucleotides of Streptococcus pneumoniae origin isolated by using part or all of the fragments in question as a probe or primer.

Preferred DFs of the present invention comprise at least about 17, preferably at least about 20, and more preferably at least about 50 contiguous nucleotides within an ORF set out in Tables 1-3. Most highly preferred DFs specifically hybridize to a polynucleotide containing the sequence of the ORF from which they are derived. Specific hybridization occurs even under stringent conditions defined elsewhere herein.

Each of the ORFs of the Streptococcus pneumoniae genome disclosed in Tables 1, 2 and 3, and the EMFs found 5′ to the ORFs, can be used as polynucleotide reagents in numerous ways. For example, the sequences can be used as diagnostic probes or diagnostic amplification primers to detect the presence of a specific microbe in a sample, particularly Streptococcus pneumoniae. Especially preferred in this regard are ORFs such as those of Table 3, which do not match previously characterized sequences from other organisms and thus are most likely to be highly selective for Streptococcus pneumoniae. Also particularly preferred are ORFs that can be used to distinguish between strains of Streptococcus pneumoniae, particularly those that distinguish medically important strain, such as drug-resistant strains.

In addition, the fragments of the present invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA. Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Information from the sequences of the present invention can be used to design antisense and triple helix-forming oligonucleotides. Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription, for triple-helix formation, or to the mRNA itself, for antisense inhibition. Both techniques have been demonstrated to be effective in model systems, and the requisite techniques are well known and involve routine procedures. Triple helix techniques are discussed in, for example, Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991). Antisense techniques in general are discussed in, for instance, Okano, J. Neurochem. 56:560 (1991) and Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)).

The present invention further provides recombinant constructs comprising one or more fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention. Certain preferred recombinant constructs of the present invention comprise a vector, such as a plasmid or viral vector, into which a fragment of the Streptococcus pneumoniae genome has been inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs of the present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. For vectors comprising the EMFs of the present invention, the vector may further comprise a marker sequence or heterologous ORF operably linked to the EMF.

Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs of the present invention. The following vectors are provided by way of example. Useful bacterial vectors include phagescript, PsiX174, pBluescript SK, pBS KS, pNH8a, pNH16a, pNH18a, pNH46a (available from Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (available from Pharmacia). Useful eukaryotic vectors include pWLneo, pSV2cat, pOG44, pXT1, pSG (available from Stratagene) pSVK3, pBPV, pMSG, pSVL (available from Pharmacia).

Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lacI, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art.

The present invention further provides host cells containing any one of the isolated fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention, wherein the fragment has been introduced into the host cell using known methods. The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or a procaryotic cell, such as a bacterial cell.

A polynucleotide of the present invention, such as a recombinant construct comprising an ORF of the present invention, may be introduced into the host by a variety of well established techniques that are standard in the art, such as calcium phosphate transfection, DEAE, dextran mediated transfection and electroporation, which are described in, for instance, Davis, L. et al., BASIC METHODS IN MOLECULAR BIOLOGY (1986).

A host cell containing one of the fragments of the Streptococcus pneumoniae genomic fragments and contigs of the present invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to produce a heterologous protein under the control of the EMF.

The present invention further provides isolated polypeptides encoded by the nucleic acid fragments of the present invention or by degenerate variants of the nucleic acid fragments of the present invention. By “degenerate variant” is intended nucleotide fragments which differ from a nucleic acid fragment of the present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy of the Genetic Code, encode an identical polypeptide sequence.

Preferred nucleic acid fragments of the present invention are the ORFs and subfragments thereof depicted in Tables 2 and 3 which encode proteins.

A variety of methodologies known in the art can be utilized to obtain any one of the isolated polypeptides or proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. Such short fragments as may be obtained most readily by synthesis are useful, for example, in generating antibodies against the native polypeptide, as discussed further below.

In an alternative method, the polypeptide or protein is purified from bacterial cells which naturally produce the polypeptide or protein. One skilled in the art can readily employ well-known methods for isolating polypeptides and proteins to isolate and purify polypeptides or proteins of the present invention produced naturally by a bacterial strain, or by other methods. Methods for isolation and purification that can be employed in this regard include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography.

The polypeptides and proteins of the present invention also can be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. Those skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one of the polypeptides or proteins of the present invention.

Any host/vector system can be used to express one or more of the ORFs of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, CV-1 cell, COS cells, and Sf9 cells, as well as prokaryotic host such as E. coli and B. subtilis. The most preferred cells are those which do not normally express the particular polypeptide or protein or which expresses the polypeptide or protein at low natural level.

“Recombinant,” as used herein, means that a polypeptide or protein is derived from recombinant (e.g., microbial or mammalian) expression systems. “Microbial” refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, “recombinant microbial” defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g., E. coli, will be free of glycosylation modifications; polypeptides or proteins expressed in yeast will have a glycosylation pattern different from that expressed in mammalian cells.

“Nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. Generally, DNA segments encoding the polypeptides and proteins provided by this invention are assembled from fragments of the Streptococcus pneumoniae genome and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.

Recombinant expression vehicle or vector” refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. The expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic regulatory elements necessary for gene expression in the host, including elements required to initiate and maintain transcription at a level sufficient for suitable expression of the desired polypeptide, including, for example, promoters and, where necessary, an enhancer and a polyadenylation signal; (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate signals to initiate translation at the beginning of the desired coding region and terminate translation at its end. Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an N-terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.

“Recombinant expression system” means host cells which have stably integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extra chromosomally. The cells can be prokaryotic or eukaryotic. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction of the regulatory elements linked to the DNA segment or synthetic gene to be expressed.

Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described in Sambrook et al, Molecular Cloning: A Laboratory Manual, 2^(nd) Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), the disclosure of which is hereby incorporated by reference in its entirety.

Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coli and S. cerevisiae TRP1 gene, and a promoter derived from a highly expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), alpha-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product.

Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector and, when desirable, provide amplification within the host.

Suitable prokaryotic hosts for transformation include strains of E. coli, B. subtilis, Salmonella typhimurium and various species within the genera Pseudomonas and Streptomyces. Others may, also be employed as a matter of choice.

As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pKK223-3 (available form Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (available from Promega Biotec, Madison, Wis., USA). These pBR322 “backbone” sections are combined with an appropriate promoter and the structural sequence to be expressed.

Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter, where it is inducible, is derepressed or induced by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period to provide for expression of the induced gene product. Thereafter cells are typically harvested, generally by centrifugation, disrupted to release expressed protein, generally by physical or chemical means, and the resulting crude extract is retained for further purification.

Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described in Gluzman, Cell 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines.

Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.

Recombinant polypeptides and proteins produced in bacterial culture is usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps.

The present invention further includes isolated polypeptides, proteins and nucleic acid molecules which are substantially equivalent to those herein described. As used herein, substantially equivalent can refer both to nucleic acid and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between reference and subject sequences. For purposes of the present invention, sequences having equivalent biological activity, and equivalent expression characteristics are considered substantially equivalent. For purposes of determining equivalence, truncation of the mature sequence should be disregarded.

The invention further provides methods of obtaining homologs from other strains of Streptococcus pneumoniae, of the fragments of the Streptococcus pneumoniae genome of the present invention and homologs of the proteins encoded by the ORFs of the present invention. As used herein, a sequence or protein of Streptococcus pneumoniae is defined as a homolog of a fragment of the Streptococcus pneumoniae fragments or contigs or a protein encoded by one of the ORFs of the present invention, if it shares significant homology to one of the fragments of the Streptococcus pneumoniae genome of the present invention or a protein encoded by one of the ORFs of the present invention. Specifically, by using the sequence disclosed herein as a probe or as primers, and techniques such as PCR cloning and colony/plaque hybridization, one skilled in the art can obtain homologs.

As used herein, two nucleic acid molecules or proteins are said to “share significant homology” if the two contain regions which possess greater than 85% sequence (amino acid or nucleic acid) homology. Preferred homologs in this regard are those with more than 90% homology. Especially preferred are those with 93% or more homology. Among especially preferred homologs those with 95% or more homology are particularly preferred. Very particularly preferred among these are those with 97% and even more particularly preferred among those are homologs with 99% or more homology. The most preferred homologs among these are those with 99.9% homology or more. It will be understood that, among measures of homology, identity is particularly preferred in this regard.

Region specific primers or probes derived from the nucleotide sequence provided in SEQ ID NOS:1-391 or from a nucleotide sequence at least 95%, particularly at least 99%, especially at least 99.5% identical to a sequence of SEQ ID NOS:1-391 can be used to prime DNA synthesis and PCR amplification, as well as to identify colonies containing cloned DNA encoding a homolog. Methods suitable to this aspect of the present invention are well known and have been described in great detail in many publications such as, for example, Innis et al., PCR Protocols, Academic Press, San Diego, Calif. (1990)).

When using primers derived from SEQ ID NOS:1-391 or from a nucleotide sequence having an aforementioned identity to a sequence of SEQ ID NOS:1-391, one skilled in the art will recognize that by employing high stringency conditions (e.g., annealing at 50-60° C. in 6×SSC and 50% formamide, and washing at 50-65° C. in 0.5×SSC) only sequences which are greater than 75% homologous to the primer will be amplified. By employing lower stringency conditions (e.g., hybridizing at 35-37° C. in 5×SSC and 40-45% formamide, and washing at 42° C. in 0.5×SSC), sequences which are greater than 40-50% homologous to the primer will also be amplified.

When using DNA probes derived from SEQ ID NOS:1-391, or from a nucleotide sequence having an aforementioned identity to a sequence of SEQ ID NOS:1-391, for colony/plaque hybridization, one skilled in the art will recognize that by employing high stringency conditions (e.g., hybridizing at 50-65° C. in 5×SSC and 50% formamide, and washing at 50-65° C. in 0.5×SSC), sequences having regions which are greater than 90% homologous to the probe can be obtained, and that by employing lower stringency conditions (e.g., hybridizing at 35-37° C. in 5×SSC and 40-45% formamide, and washing at 42° C. in 0.5×SSC), sequences having regions which are greater than 35-45% homologous to the probe will be obtained.

Any organism can be used as the source for homologs of the present invention so long as the organism naturally expresses such a protein or contains genes encoding the same. The most preferred organism for isolating homologs are bacteria which are closely related to Streptococcus pneumoniae.

Illustrative Uses of Compositions of the Invention

Each ORF provided in Tables 1 and 2 is identified with a function by homology to a known gene or polypeptide. As a result, one skilled in the art can use the polypeptides of the present invention for commercial, therapeutic and industrial purposes consistent with the type of putative identification of the polypeptide. Such identifications permit one skilled in the art to use the Streptococcus pneumoniae ORFs in a manner similar to the known type of sequences for which the identification is made; for example, to ferment a particular sugar source or to produce a particular metabolite. A variety of reviews illustrative of this aspect of the invention are available, including the following reviews on the industrial use of enzymes, for example, BIOCHEMICAL ENGINEERING AND BIOTECHNOLOGY HANDBOOK, 2nd Ed., MacMillan Publications, Ltd. NY (1991) and BIOCATALYSTS IN ORGANIC SYNTHESES, Tramper et al., Eds., Elsevier Science Publishers, Amsterdam, The Netherlands (1985). A variety of exemplary uses that illustrate this and similar aspects of the present invention are discussed below.

1. Biosynthetic Enzymes

Open reading frames encoding proteins involved in mediating the catalytic reactions involved in intermediary and macromolecular metabolism, the biosynthesis of small molecules, cellular processes and other functions includes enzymes involved in the degradation of the intermediary products of metabolism, enzymes involved in central intermediary metabolism, enzymes involved in respiration, both aerobic and anaerobic, enzymes involved in fermentation, enzymes involved in ATP proton motor force conversion, enzymes involved in broad regulatory function, enzymes involved in amino acid synthesis, enzymes involved in nucleotide synthesis, enzymes involved in cofactor and vitamin synthesis, can be used for industrial biosynthesis.

The various metabolic pathways present in Streptococcus pneumoniae can be identified based on absolute nutritional requirements as well as by examining the various enzymes identified in Table 1-3 and SEQ ID NOS:1-391.

Of particular interest are polypeptides involved in the degradation of intermediary metabolites as well as non-macromolecular metabolism. Such enzymes include amylases, glucose oxidases, and catalase.

Proteolytic enzymes are another class of commercially important enzymes. Proteolytic enzymes find use in a number of industrial processes including the processing of flax and other vegetable fibers, in the extraction, clarification and depectinization of fruit juices, in the extraction of vegetables' oil and in the maceration of fruits and vegetables to give unicellular fruits. A detailed review of the proteolytic enzymes used in the food industry is provided in Rombouts et al., Symbiosis 21:79 (1986) and Voragen et al. in Biocatalysts In Agricultural Biotechnology, Whitaker et al., Eds., American Chemical Society Symposium Series 389:93 (1989).

The metabolism of sugars is an important aspect of the primary metabolism of Streptococcus pneumoniae. Enzymes involved in the degradation of sugars, such as, particularly, glucose, galactose, fructose and xylose, can be used in industrial fermentation. Some of the important sugar transforming enzymes, from a commercial viewpoint, include sugar isomerases such as glucose isomerase. Other metabolic enzymes have found commercial use such as glucose oxidases which produces ketogulonic acid (KGA). KGA is an intermediate in the commercial production of ascorbic acid using the Reichstein's procedure, as described in Krueger et al, Biotechnology 6(A), Rhine et al., Eds., Verlag Press, Weinheim, Germany (1984).

Glucose oxidase (GOD) is commercially available and has been used in purified form as well as in an immobilized form for the deoxygenation of beer. See, for instance, Hartmeir et al., Biotechnology Letters 1:21 (1979). The most important application of GOD is the industrial scale fermentation of gluconic acid. Market for gluconic acids which are used in the detergent, textile, leather, photographic, pharmaceutical, food, feed and concrete industry, as described, for example, in Bigelis et al., beginning on page 357 in GENE MANIPULATIONS AND FUNGI; Benett et al., Eds., Academic Press, New York (1985). In addition to industrial applications, GOD has found applications in medicine for quantitative determination of glucose in body fluids recently in biotechnology for analyzing syrups from starch and cellulose hydrosylates. This application is described in Owusu et al, Biochem. et Biophysica. Acta. 872:83 (1986), for instance.

The main sweetener used in the world today is sugar which comes from sugar beets and sugar cane. In the field of industrial enzymes, the glucose isomerase process shows the largest expansion in the market today. Initially, soluble enzymes were used and later immobilized enzymes were developed (Krueger et al., Biotechnology, The Textbook of Industrial Microbiology, Sinauer Associated Incorporated, Sunderland, Mass. (1990)). Today, the use of glucose-produced high fructose syrups is by far the largest industrial business using immobilized enzymes. A review of the industrial use of these enzymes is provided by Jorgensen, Starch 40:307 (1988).

Proteinases, such as alkaline serine proteinases, are used as detergent additives and thus represent one of the largest volumes of microbial enzymes used in the industrial sector. Because of their industrial importance, there is a large body of published and unpublished information regarding the use of these enzymes in industrial processes. (See Faultman et al, Acid Proteases Structure Function and Biology, Tang, J., ed., Plenum Press, New York (1977) and Godfrey et al., Industrial Enzymes, MacMillan Publishers, Surrey, UK (1983) and Hepner et al., Report Industrial Enzymes by 1990, Hel Hepner & Associates, London (1986)).

Another class of commercially usable proteins of the present invention are the microbial lipases, described by, for instance, Macrae et al., Philosophical Transactions of the Chiral Society of London 310:227 (1985) and Poserke, Journal of the American Oil Chemist Society 61:1758 (1984). A major use of lipases is in the fat and oil industry for the production of neutral glycerides using lipase catalyzed inter-esterification of readily available triglycerides. Application of lipases include the use as a detergent additive to facilitate the removal of fats from fabrics in the course of the washing procedures.

The use of enzymes, and in particular microbial enzymes, as catalyst for key steps in the synthesis of complex organic molecules is gaining popularity at a great rate. One area of great interest is the preparation of chiral intermediates. Preparation of chiral intermediates is of interest to a wide range of synthetic chemists particularly those scientists involved with the preparation of new pharmaceuticals, agrochemicals, fragrances and flavors. (See Davies et al., Recent Advances in the Generation of Chiral Intermediates Using Enzymes, CRC Press, Boca Raton, Fla. (1990)). The following reactions catalyzed by enzymes are of interest to organic chemists: hydrolysis of carboxylic acid esters, phosphate esters, amides and nitrites, esterification reactions, trans-esterification reactions, synthesis of amides, reduction of alkanones and oxoalkanates, oxidation of alcohols to carbonyl compounds, oxidation of sulfides to sulfoxides, and carbon bond forming reactions such as the aldol reaction.

When considering the use of an enzyme encoded by one of the ORFs of the present invention for biotransformation and organic synthesis it is sometimes necessary to consider the respective advantages and disadvantages of using a microorganism as opposed to an isolated enzyme. Pros and cons of using a whole cell system on the one hand or an isolated partially purified enzyme on the other hand, has been described in detail by Bud et al., Chemistry in Britain (1987), p. 127.

Amino transferases, enzymes involved in the biosynthesis and metabolism of amino acids, are useful in the catalytic production of amino acids. The advantages of using microbial based enzyme systems is that the amino transferase enzymes catalyze the stereo-selective synthesis of only L-amino acids and generally possess uniformly high catalytic rates. A description of the use of amino transferases for amino acid production is provided by Roselle-David, Methods of Enzymology 136:479 (1987).

Another category of useful proteins encoded by the ORFs of the present invention include enzymes involved in nucleic acid synthesis, repair, and recombination.

2. Generation of Antibodies

As described here, the proteins of the present invention, as well as homologs thereof, can be used in a variety of procedures and methods known in the art which are currently applied to other proteins. The proteins of the present invention can further be used to generate an antibody which selectively binds the protein. Such antibodies can be either monoclonal or polyclonal antibodies, as well fragments of these antibodies, and humanized forms.

The invention further provides antibodies which selectively bind to one of the proteins of the present invention and hybridomas which produce these antibodies. A hybridoma is an immortalized cell line which is capable of secreting a specific monoclonal antibody.

In general, techniques for preparing polyclonal and monoclonal antibodies as well as hybridomas capable of producing the desired antibody are well known in the art (Campbell, A. M., Monoclonal Antibody Technology: Laboratory Techniques In Biochemistry And Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984); St. Groth et al., J. Immunol. Methods 35: 1-21 (1980), Kohler and Milstein, Nature 256:495-497 (1975)), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today 4:72 (1983), pgs. 77-96 of Cole et al, in Monoclonal Antibodies And Cancer Therapy, Alan R. Liss, Inc. (1985)). Any animal (mouse, rabbit, etc.) which is known to produce antibodies can be immunized with the pseudogene polypeptide. Methods for immunization are well known in the art. Such methods include subcutaneous or interperitoneal injection of the polypeptide. One skilled in the art will recognize that the amount of the protein encoded by the ORF of the present invention used for immunization will vary based on the animal which is immunized, the antigenicity of the peptide and the site of injection.

The protein which is used as an immunogen may be modified or administered in an adjuvant in order to increase the protein's antigenicity. Methods of increasing the antigenicity of a protein are well known in the art and include, but are not limited to coupling the antigen with a heterologous protein (such as globulin or galactosidase) or through the inclusion of an adjuvant during immunization.

For monoclonal antibodies, spleen cells from the immunized animals are removed, fused with myeloma cells, such as SP2/0-Ag14 myeloma cells, and allowed to become monoclonal antibody producing hybridoma cells.

Any one of a number of methods well known in the art can be used to identify the hybridoma cell which produces an antibody with the desired characteristics. These include screening the hybridomas with an ELISA assay, western blot analysis, or radioimmunoassay (Lutz et al., Exp. Cell Res. 175: 109-124 (1988)).

Hybridomas secreting the desired antibodies are cloned and the class and subclass is determined using procedures known in the art (Campbell, A. M., Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984)).

Techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778) can be adapted to produce single chain antibodies to proteins of the present invention.

For polyclonal antibodies, antibody containing antisera is isolated from the immunized animal and is screened for the presence of antibodies with the desired specificity using one of the above-described procedures.

The present invention further provides the above-described antibodies in detectably labeled form. Antibodies can be detectably labeled through the use of radioisotopes, affinity labels (such as biotin, avidin, etc.), enzymatic labels (such as horseradish peroxidase, alkaline phosphatase, etc.) fluorescent labels (such as FITC or rhodamine, etc.), paramagnetic atoms, etc. Procedures for accomplishing such labeling are well-known in the art, for example see Sternberger et al., J. Histochem. Cytochem. 18:315 (1970); Bayer, E. A. et al., Meth. Enzym. 62:308 (1979); Engval, E. et al., Immunol. 109:129 (1972); Goding, J. W., J. Immunol. Meth. 13:215 (1976)).

The labeled antibodies of the present invention can be used for in vitro, in vivo, and in situ assays to identify cells or tissues in which a fragment of the Streptococcus pneumoniae genome is expressed.

The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and sepharose, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D. M. et al., “Handbook of Experimental Immunology” 4th Ed., Blackwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W. D. et al., Meth. Enzym. 34 Academic Press, N.Y. (1974)). The immobilized antibodies of the present invention can be used for in vitro, in vivo, and in situ assays as well as for immunoaffinity purification of the proteins of the present invention.

3. Diagnostic Assays and Kits

The present invention further provides methods to identify the expression of one of the ORFs of the present invention, or homolog thereof, in a test sample, using one of the DFs or antibodies of the present invention.

In detail, such methods comprise incubating a test sample with one or more of the antibodies or one or more of the DFs of the present invention and assaying for binding of the DFs or antibodies to components within the test sample.

Conditions for incubating a DF or antibody with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the DF or antibody used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the DFs or antibodies of the present invention. Examples of such assays can be found in Chard, T., An Introduction to Radioimmunoassay and Related Techniques, Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G. R. et al., Techniques in Immunocytochemistry, Academic Press, Orlando, Fla. Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of Enzyme Immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1985).

The test samples of the present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized.

In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention.

Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the DFs or antibodies of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound DF or antibody.

In detail, a compartmentalized kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or DF.

Types of detection reagents include labeled nucleic acid probes, labeled secondary antibodies, or in the alternative, if the primary antibody is labeled, the enzymatic, or antibody binding reagents which are capable of reacting with the labeled antibody. One skilled in the art will readily recognize that the disclosed DFs and antibodies of the present invention can be readily incorporated into one of the established kit formats which are well known in the art.

4. Screening Assay for Binding Agents

Using the isolated proteins of the present invention, the present invention further provides methods of obtaining and identifying agents which bind to a protein encoded by one of the ORFs of the present invention or to one of the fragments and the Streptococcus pneumoniae fragment and contigs herein described.

In general, such methods comprise steps of:

contacting an agent with an isolated protein encoded by one of the ORFs of the present invention, or an isolated fragment of the Streptococcus pneumoniae genome; and

determining whether the agent binds to said protein or said fragment.

The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques.

For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF of the present invention.

Alternatively, agents may be rationally selected or designed. As used herein, an agent is said to be “rationally selected or designed” when the agent is chosen based on the configuration of the particular protein. For example, one skilled in the art can readily adapt currently available procedures to generate peptides, pharmaceutical agents and the like capable of binding to a specific peptide sequence in order to generate rationally designed antipeptide peptides, for example see Hurby et al., “Application of Synthetic Peptides: Antisense Peptides,” in Synthetic Peptides, A User's Guide, W. H. Freeman, NY (1992), pp. 289-307, and Kaspczak et al., Biochemistry 28:9230-8 (1989), or pharmaceutical agents, or the like.

In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one of the ORFs or EMFs of the present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control.

One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulfhydryl or polymeric derivatives which have base attachment capacity.

Agents suitable for use in these methods usually contain 20 to 40 bases and are designed to be complementary to a region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991)) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)). Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention can be used to design antisense and triple helix-forming oligonucleotides, and other DNA binding agents.

5. Pharmaceutical Compositions and Vaccines

The present invention further provides pharmaceutical agents which can be used to modulate the growth or pathogenicity of Streptococcus pneumoniae, or another related organism, in vivo or in vitro. As used herein, a “pharmaceutical agent” is defined as a composition of matter which can be formulated using known techniques to provide a pharmaceutical compositions. As used herein, the “pharmaceutical agents of the present invention” refers the pharmaceutical agents which are derived from the proteins encoded by the ORFs of the present invention or are agents which are identified using the herein described assays.

As used herein, a pharmaceutical agent is said to “modulate the growth pathogenicity of Streptococcus pneumoniae or a related organism, in vivo or in vitro,” when the agent reduces the rate of growth, rate of division, or viability of the organism in question. The pharmaceutical agents of the present invention can modulate the growth or pathogenicity of an organism in many fashions, although an understanding of the underlying mechanism of action is not needed to practice the use of the pharmaceutical agents of the present invention. Some agents will modulate the growth by binding to an important protein thus blocking the biological activity of the protein, while other agents may bind to a component of the outer surface of the organism blocking attachment or rendering the organism more prone to act the bodies nature immune system. Alternatively, the agent may comprise a protein encoded by one of the ORFs of the present invention and serve as a vaccine. The development and use of a vaccine based on outer membrane components are well known in the art.

As used herein, a “related organism” is a broad term which refers to any organism whose growth can be modulated by one of the pharmaceutical agents of the present invention. In general, such an organism will contain a homolog of the protein which is the target of the pharmaceutical agent or the protein used as a vaccine. As such, related organisms do not need to be bacterial but may be fungal or viral pathogens.

The pharmaceutical agents and compositions of the present invention may be administered in a convenient manner, such as by the oral, topical, intravenous, intraperitoneal, intramuscular, subcutaneous, intranasal or intradermal routes. The pharmaceutical compositions are administered in an amount which is effective for treating and/or prophylaxis of the specific indication. In general, they are administered in an amount of at least about 1 mg/kg body weight and in most cases they will be administered in an amount not in excess of about 1 g/kg body weight per day. In most cases, the dosage is from about 0.1 mg/kg to about 10 g/kg body weight daily, taking into account the routes of administration, symptoms, etc.

The agents of the present invention can be used in native form or can be modified to form a chemical derivative. As used herein, a molecule is said to be a “chemical derivative” of another molecule when it contains additional chemical moieties not normally a part of the molecule. Such moieties may improve the molecule's solubility, absorption, biological half life, etc. The moieties may alternatively decrease the toxicity of the molecule, eliminate or attenuate any undesirable side effect of the molecule, etc. Moieties capable of mediating such effects are disclosed in, among other sources, REMINGTON'S PHARMACEUTICAL SCIENCES (1980) cited elsewhere herein.

For example, such moieties may change an immunological character of the functional derivative, such as affinity for a given antibody. Such changes in immunomodulation activity are measured by the appropriate assay, such as a competitive type immunoassay. Modifications of such protein properties as redox or thermal stability, biological half-life, hydrophobicity, susceptibility to proteolytic degradation or the tendency to aggregate with carriers or into multimers also may be effected in this way and can be assayed by methods well known to the skilled artisan.

The therapeutic effects of the agents of the present invention may be obtained by providing the agent to a patient by any suitable means (e.g., inhalation, intravenously, intramuscularly, subcutaneously, enterally, or parenterally). It is preferred to administer the agent of the present invention so as to achieve an effective concentration within the blood or tissue in which the growth of the organism is to be controlled. To achieve an effective blood concentration, the preferred method is to administer the agent by injection. The administration may be by continuous infusion, or by single or multiple injections.

In providing a patient with one of the agents of the present invention, the dosage of the administered agent will vary depending upon such factors as the patient's age, weight, height, sex, general medical condition, previous medical history, etc. In general, it is desirable to provide the recipient with a dosage of agent which is in the range of from about 1 pg/kg to 10 mg/kg (body weight of patient), although a lower or higher dosage may be administered. The therapeutically effective dose can be lowered by using combinations of the agents of the present invention or another agent.

As used herein, two or more compounds or agents are said to be administered “in combination” with each other when either (1) the physiological effects of each compound, or (2) the serum concentrations of each compound can be measured at the same time. The composition of the present invention can be administered concurrently with, prior to, or following the administration of the other agent.

The agents of the present invention are intended to be provided to recipient subjects in an amount sufficient to decrease the rate of growth (as defined above) of the target organism.

The administration of the agent(s) of the invention may be for either a “prophylactic” or “therapeutic” purpose. When provided prophylactically, the agent(s) are provided in advance of any symptoms indicative of the organisms growth. The prophylactic administration of the agent(s) serves to prevent, attenuate, or decrease the rate of onset of any subsequent infection. When provided therapeutically, the agent(s) are provided at (or shortly after) the onset of an indication of infection. The therapeutic administration of the compound(s) serves to attenuate the pathological symptoms of the infection and to increase the rate of recovery.

The agents of the present invention are administered to a subject, such as a mammal, or a patient, in a pharmaceutically acceptable form and in a therapeutically effective concentration. A composition is said to be “pharmacologically acceptable” if its administration can be tolerated by a recipient patient. Such an agent is said to be administered in a “therapeutically effective amount” if the amount administered is physiologically significant. An agent is physiologically significant if its presence results in a detectable change in the physiology of a recipient patient.

The agents of the present invention can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby these materials, or their functional derivatives, are combined in a mixture with a pharmaceutically acceptable carrier vehicle. Suitable vehicles and their formulation, inclusive of other human proteins, e.g., human serum albumin, are described, for example, in REMINGTON'S PHARMACEUTICAL SCIENCES, 16^(th) Ed., Osol, A., Ed., Mack Publishing, Easton Pa. (1980). In order to form a pharmaceutically acceptable composition suitable for effective administration, such compositions will contain an effective amount of one or more of the agents of the present invention, together with a suitable amount of carrier vehicle.

Additional pharmaceutical methods may be employed to control the duration of action. Control release preparations may be achieved through the use of polymers to complex or absorb one or more of the agents of the present invention. The controlled delivery may be effectuated by a variety of well known techniques, including formulation with macromolecules such as, for example, polyesters, polyamino acids, polyvinyl, pyrrolidone, ethylenevinylacetate, methylcellulose, carboxymethylcellulose, or protamine, sulfate, adjusting the concentration of the macromolecules and the agent in the formulation, and by appropriate use of methods of incorporation, which can be manipulated to effectuate a desired time course of release. Another possible method to control the duration of action by controlled release preparations is to incorporate agents of the present invention into particles of a polymeric material such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylene vinylacetate copolymers. Alternatively, instead of incorporating these agents into polymeric particles, it is possible to entrap these materials in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization with, for example, hydroxymethylcellulose or gelatine-microcapsules and poly(methylmethacylate) microcapsules, respectively, or in colloidal drug delivery systems, for example, liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules or in macroemulsions. Such techniques are disclosed in REMINGTON'S PHARMACEUTICAL SCIENCES (1980).

The invention further provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.

In addition, the agents of the present invention may be employed in conjunction with other therapeutic compounds.

6. Shot-Gun Approach to Megabase DNA Sequencing

The present invention further demonstrates that a large sequence can be sequenced using a random shotgun approach. This procedure, described in detail in the examples that follow, has eliminated the up front cost of isolating and ordering overlapping or contiguous subclones prior to the start of the sequencing protocols.

Certain aspects of the present invention are described in greater detail in the examples that follow. The examples are provided by way of illustration. Other aspects and embodiments of the present invention are contemplated by the inventors, as will be clear to those of skill in the art from reading the present disclosure.

ILLUSTRATIVE EXAMPLES

Libraries and Sequencing

1. Shotgun Sequencing Probability Analysis

The overall strategy for a shotgun approach to whole genome sequencing follows from the Lander and Waterman (Landerman and Waterman, Genomics 2:231 (1988)) application of the equation for the Poisson distribution. According to this treatment, the probability, P, that any given base in a sequence of size L, in nucleotides, is not sequenced after a certain amount, n, in nucleotides, of random sequence has been determined can be calculated by the equation P=e^(−m), where m is L/n, the fold coverage. For instance, for a genome of 2.8 Mb, m=1 when 2.8 Mb of sequence has been randomly generated (1× coverage). At that point, P=e⁻¹=0.37. The probability that any given base has not been sequenced is the same as the probability that any region of the whole sequence L has not been determined and, therefore, is equivalent to the fraction of the whole sequence that has yet to be determined. Thus, at one-fold coverage, approximately 37% of a polynucleotide of size L, in nucleotides has not been sequenced. When 14 Mb of sequence has been generated, coverage is 5× for a 2.8 Mb and the unsequenced fraction drops to 0.0067 or 0.67%. 5× coverage of a 2.8 Mb sequence can be attained by sequencing approximately 17,000 random clones from both insert ends with an average sequence read length of 410 bp.

Similarly, the total gap length, G, is determined by the equation G=Le^(−m), and the average gap size, g, follows the equation, g=L/n. Thus, 5× coverage leaves about 240 gaps averaging about 82 bp in size in a sequence of a polynucleotide 2.8 Mb long.

The treatment above is essentially that of Lander and Waterman, Genomics 2: 231 (1988).

2. Random Library Construction

In order to approximate the random model described above during actual sequencing, a nearly ideal library of cloned genomic fragments is required. The following library construction procedure was developed to achieve this end.

Streptococcus pneumoniae DNA is prepared by phenol extraction. A mixture containing 200 μg DNA in 1.0 ml of 300 mM sodium acetate, 10 mM Tris-HCl, 1 mM Na-EDTA, 50% glycerol is processed through a nebulizer (IPI Medical Products) with a stream of nitrogen adjusted to 35 Kpa for 2 minutes. The sonicated DNA is ethanol precipitated and redissolved in 500 μl TE buffer.

To create blunt-ends, a 100 μl aliquot of the resuspended DNA is digested with 5 units of BAL31 nuclease (New England BioLabs) for 10 min at 30° C. in 200 μl BAL31 buffer. The digested DNA is phenol-extracted, ethanol-precipitated, redissolved in 100 μl TE buffer, and then size-fractionated by electrophoresis through a 1.0% low melting temperature agarose gel. The section containing DNA fragments 1.6-2.0 kb in size is excised from the gel, and the LGT agarose is melted and the resulting solution is extracted with phenol to separate the agarose from the DNA. DNA is ethanol precipitated and redissolved in 20 μl of TE buffer for ligation to vector.

A two-step ligation procedure is used to produce a plasmid library with 97% inserts, of which >99% were single inserts. The first ligation mixture (50 ul) contains 2 μg of DNA fragments, 2 μg pUC18 DNA (Pharmacia) cut with SmaI and dephosphorylated with bacterial alkaline phosphatase, and 10 units of T4 ligase (GIBCO/BRL) and is incubated at 14° C. for 4 hr. The ligation mixture then is phenol extracted and ethanol precipitated, and the precipitated DNA is dissolved in 20 μl TE buffer and electrophoresed on a 1.0% low melting agarose gel. Discrete bands in a ladder are visualized by ethidium bromide-staining and UV illumination and identified by size as insert (I), vector (v), v+I, v+2i, v+3i, etc. The portion of the gel containing v+I DNA is excised and the v+I DNA is recovered and resuspended into 20 μl TE. The v+I DNA then is blunt-ended by T4 polymerase treatment for 5 min. at 37° C. in a reaction mixture (50 ul) containing the v+I linears, 500 μM each of the 4 dNTPs, and 9 units of T4 polymerase (New England BioLabs), under recommended buffer conditions. After phenol extraction and ethanol precipitation the repaired v+I linears are dissolved in 20 μl TE. The final ligation to produce circles is carried out in a 50 μl reaction containing 5 μl of v+I linears and 5 units of T4 ligase at 14° C. overnight. After 10 min. at 70° C. the following day, the reaction mixture is stored at −20° C.

This two-stage procedure results in a molecularly random collection of single-insert plasmid recombinants with minimal contamination from double-insert chimeras (<1%) or free vector (<3%).

Since deviation from randomness can arise from propagation the DNA in the host, E. coli host cells deficient in all recombination and restriction functions (A. Greener, Strategies 3 (1):5 (1990)) are used to prevent rearrangements, deletions, and loss of clones by restriction. Furthermore, transformed cells are plated directly on antibiotic diffusion plates to avoid the usual broth recovery phase which allows multiplication and selection of the most rapidly growing cells.

Plating is carried out as follows. A 100 μl aliquot of Epicurian Coli SURE TI Supercompetent Cells (Stratagene 200152) is thawed on ice and transferred to a chilled Falcon 2059 tube on ice. A 1.7 μl aliquot of 1.42 M beta-mercaptoethanol is added to the aliquot of cells to a final concentration of 25 mM. Cells are incubated on ice for 10 min. A 1 μl aliquot of the final ligation is added to the cells and incubated on ice for 30 min. The cells are heat pulsed for 30 sec. at 42° C. and placed back on ice for 2 min. The outgrowth period in liquid culture is eliminated from this protocol in order to minimize the preferential growth of any given transformed cell. Instead the transformation mixture is plated directly on a nutrient rich SOB plate containing a 5 ml bottom layer of SOB agar (5% SOB agar: 20 g tryptone, 5 g yeast extract, 0.5 g NaCl, 1.5% Difco Agar per liter of media). The 5 ml bottom layer is supplemented with 0.4 ml of 50 mg/ml ampicillin per 100 ml SOB agar. The 15 ml top layer of SOB agar is supplemented with 1 ml X-Gal (2%), 1 ml MgCl (1 M), and 1 ml MgSO/100 ml SOB agar. The 15 ml top layer is poured just prior to plating. Our titer is approximately 100 colonies/10 μl aliquot of transformation.

All colonies are picked for template preparation regardless of size. Thus, only clones lost due to “poison” DNA or deleterious gene products are deleted from the library, resulting in a slight increase in gap number over that expected.

3. Random DNA Sequencing

High quality double stranded DNA plasmid templates are prepared using a “boiling bead” method developed in collaboration with Advanced Genetic Technology Corp. (Gaithersburg, Md.) (Adams et al., Science 252:1651 (1991); Adams et al., Nature 355:632 (1992)). Plasmid preparation is performed in a 96-well format for all stages of DNA preparation from bacterial growth through final DNA purification. Template concentration is determined using Hoechst Dye and a Millipore Cytofluor. DNA concentrations are not adjusted, but low-yielding templates are identified where possible and not sequenced.

Templates are also prepared from two Streptococcus pneumoniae lambda genomic libraries. An amplified library is constructed in the vector Lambda GEM-12 (Promega) and an unamplified library is constructed in Lambda DASH TI (Stratagene). In particular, for the unamplified lambda library, Streptococcus pneumoniae DNA (>100 kb) is partially digested in a reaction mixture (200 ul) containing 50 μg DNA, 1× Sau3AI buffer, 20 units Sau3AI for 6 min. at 23° C. The digested DNA was phenol-extracted and electrophoresed on a 0.5% low melting agarose gel at 2V/cm for 7 hours. Fragments from 15 to 25 kb are excised and recovered in a final volume of 6 ul. One μl of fragments is used with 1 μl of DASHII vector (Stratagene) in the recommended ligation reaction. One μl of the ligation mixture is used per packaging reaction following the recommended protocol with the Gigapack II XL Packaging Extract (Stratagene, #227711). Phage are plated directly without amplification from the packaging mixture (after dilution with 500 μl of recommended SM buffer and chloroform treatment). Yield is about 2.5×10³ pfu/ul. The amplified library is prepared essentially as above except the lambda GEM-12 vector is used. After packaging, about 3.5×10⁴ pfu are plated on the restrictive NM539 host. The lysate is harvested in 2 ml of SM buffer and stored frozen in 7% dimethylsulfoxide. The phage titer is approximately 1×10⁹ pfu/ml.

Liquid lysates (100 μl) are prepared from randomly selected plaques (from the unamplified library) and template is prepared by long-range PCR using T7 and T3 vector-specific primers.

Sequencing reactions are carried out on plasmid and/or PCR templates using the AB Catalyst LabStation with Applied Biosystems PRISM Ready Reaction Dye Primer Cycle Sequencing Kits for the M13 forward (M13-21) and the M13 reverse (M13RP1) primers (Adams et al., Nature 368:474 (1994)). Dye terminator sequencing reactions are carried out on the lambda templates on a Perkin-Elmer 9600 Thermocycler using the Applied Biosystems Ready Reaction Dye Terminator Cycle Sequencing kits. T7 and SP6 primers are used to sequence the ends of the inserts from the Lambda GEM-12 library and T7 and T3 primers are used to sequence the ends of the inserts from the Lambda DASH II library. Sequencing reactions are performed by eight individuals using an average of fourteen AB 373 DNA Sequencers per day. All sequencing reactions are analyzed using the Stretch modification of the AB 373, primarily using a 34 cm well-to-read distance. The overall sequencing success rate very approximately is about 85% for M13-21 and M13RP1 sequences and 65% for dye-terminator reactions. The average usable read length is 485 bp for M13-21 sequences, 445 bp for M13RP1 sequences, and 375 bp for dye-terminator reactions.

Richards et al., Chapter 28 in AUTOMATED DNA SEQUENCING AND ANALYSIS, M. D. Adams, C. Fields, J. C. Venter, Eds., Academic Press, London, (1994) described the value of using sequence from both ends of sequencing templates to facilitate ordering of contigs in shotgun assembly projects of lambda and cosmid clones. We balance the desirability of both-end sequencing (including the reduced cost of lower total number of templates) against shorter read-lengths for sequencing reactions performed with the M13RP1 (reverse) primer compared to the M13-21 (forward) primer. Approximately one-half of the templates are sequenced from both ends. Random reverse sequencing reactions are done based on successful forward sequencing reactions. Some M13RP1 sequences are obtained in a semi-directed fashion: M13-21: sequences pointing outward at the ends of contigs are chosen for M13RP1 sequencing in an effort to specifically order contigs.

4. Protocol for Automated Cycle Sequencing

The sequencing is carried out using ABI Catalyst robots and AB 373 Automated DNA Sequencers. The Catalyst robot is a publicly available sophisticated pipetting and temperature control robot which has been developed specifically for DNA sequencing reactions. The Catalyst combines pre-aliquoted templates and reaction mixes consisting of deoxy- and dideoxynucleotides, the thermostable Taq DNA polymerase, fluorescently-labeled sequencing primers, and reaction buffer. Reaction mixes and templates are combined in the wells of an aluminum 96-well thermocycling plate. Thirty consecutive cycles of linear amplification (i.e., one primer synthesis) steps are performed including denaturation, annealing of primer and template, and extension; i.e., DNA synthesis. A heated lid with rubber gaskets on the thermocycling plate prevents evaporation without the need for an oil overlay.

Two sequencing protocols are used: one for dye-labeled primers and a second for dye-labeled dideoxy chain terminators. The shotgun sequencing involves use of four dye-labeled sequencing primers, one for each of the four terminator nucleotide. Each dye-primer is labeled with a different fluorescent dye, permitting the four individual reactions to be combined into one lane of the 373 DNA Sequencer for electrophoresis, detection, and base-calling. ABI currently supplies pre-mixed reaction mixes in bulk packages containing all the necessary non-template reagents for sequencing. Sequencing can be done with both plasmid and PCR-generated templates with both dye-primers and dye-terminators with approximately equal fidelity, although plasmid templates generally give longer usable sequences.

Thirty-two reactions are loaded per AB373 Sequencer each day, for a total of 960 samples. Electrophoresis is run overnight following the manufacturer's protocols, and the data is collected for twelve hours. Following electrophoresis and fluorescence detection, the ABI 373 performs automatic lane tracking and base-calling. The lane-tracking is confirmed visually. Each sequence electropherogram (or fluorescence lane trace) is inspected visually and assessed for quality. Trailing sequences of low quality are removed and the sequence itself is loaded via software to a Sybase database (archived daily to 8 mm tape). Leading vector polylinker sequence is removed automatically by a software program. Average edited lengths of sequences from the standard ABI 373 are around 400 bp and depend mostly on the quality of the template used for the sequencing reaction. ABI 373 Sequencers converted to Stretch Liners provide a longer electrophoresis path prior to fluorescence detection and increase the average number of usable bases to 500-600 bp.

Informatics

1. Data Management

A number of information management systems for a large-scale sequencing lab have been developed. (For review see, for instance, Kerlavage et al., Proceedings of the Twenty-Sixth Annual Hawaii International Conference on System Sciences, IEEE Computer Society Press, Washington D.C., 585 (1993)) The system used to collect and assemble the sequence data was developed using the Sybase relational database management system and was designed to automate data flow wherever possible and to reduce user error. The database stores and correlates all information collected during the entire operation from template preparation to final analysis of the genome. Because the raw output of the ABI 373 Sequencers was based on a Macintosh platform and the data management system chosen was based on a Unix platform, it was necessary to design and implement a variety of multi-user, client-server applications which allow the raw data as well as analysis results to flow seamlessly into the database with a minimum of user effort.

2. Assembly

An assembly engine (TIGR Assembler) developed for the rapid and accurate assembly of thousands of sequence fragments was employed to generate contigs. The TIGR assembler simultaneously clusters and assembles fragments of the genome. In order to obtain the speed necessary to assemble more than 104 fragments, the algorithm builds a hash table of 12 bp oligonucleotide subsequences to generate a list of potential sequence fragment overlaps. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Beginning with a single seed sequence fragment, TIGR Assembler extends the current contig by attempting to add the best matching fragment based on oligonucleotide content. The contig and candidate fragment are aligned using a modified version of the Smith-Waterman algorithm which provides for optimal gapped alignments (Waterman, M. S., Methods in Enzymology 164:765 (1988)). The contig is extended by the fragment only if strict criteria for the quality of the match are met. The match criteria include the minimum length of overlap, the maximum length of an unmatched end, and the minimum percentage match. These criteria are automatically lowered by the algorithm in regions of minimal coverage and raised in regions with a possible repetitive element. The number of potential overlaps for each fragment determines which fragments are likely to fall into repetitive elements. Fragments representing the boundaries of repetitive elements and potentially chimeric fragments are often rejected based on partial mismatches at the ends of alignments and excluded from the current contig. TIGR Assembler is designed to take advantage of clone size information coupled with sequencing from both ends of each template. It enforces the constraint that sequence fragments from two ends of the same template point toward one another in the contig and are located within a certain range of base pairs (definable for each clone based on the known clone size range for a given library).

The process resulted in 391 contigs as represented by SEQ ID NOs:1-391.

3. Identifying Genes

The predicted coding regions of the Streptococcus pneumoniae genome were initially defined with the program GeneMark, which finds ORFs using a probabilistic classification technique. The predicted coding region sequences were used in searches against a database of all nucleotide sequences from GenBank (October, 1997), using the BLASTN search method to identify overlaps of 50 or more nucleotides with at least a 95% identity. Those ORFs with nucleotide sequence matches are shown in Table 1. The ORFs without such matches were translated to protein sequences and compared to a non-redundant database of known proteins generated by combining the Swiss-prot, PIR and GenPept databases. ORFs that matched a database protein with BLASTP probability less than or equal to 0.01 are shown in Table 2. The table also lists assigned functions based on the closest match in the databases. ORFs that did not match protein or nucleotide sequences in the databases at these levels are shown in Table 3.

Illustrative Applications

1. Production of an Antibody to a Streptococcus pneumoniae Protein

Substantially pure protein or polypeptide is isolated from the transfected or transformed cells using any one of the methods known in the art. The protein can also be produced in a recombinant prokaryotic expression system, such as E. coli, or can be chemically synthesized. Concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/ml. Monoclonal or polyclonal antibody to the protein can then be prepared as follows.

2. Monoclonal Antibody Production by Hybridoma Fusion

Monoclonal antibody to epitopes of any of the peptides identified and isolated as described can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C., Nature 256:495 (1975) or modifications of the methods thereof. Briefly, a mouse is repetitively inoculated with a few micrograms of the selected protein over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media). The successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued. Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by immunoassay procedures, such as ELISA, as originally described by Engvall, E., Meth. Enzymol. 70:419 (1980), and modified methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al., Basic Methods in Molecular Biology, Elsevier, New York. Section 21-2 (1989).

3. Polyclonal Antibody Production by Immunization

Polyclonal antiserum containing antibodies to heterogeneous epitopes of a single protein can be prepared by immunizing suitable animals with the expressed protein described above, which can be unmodified or modified to enhance immunogenicity. Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. For example, small molecules tend to be less immunogenic than others and may require the use of carriers and adjuvant. Also, host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable. An effective immunization protocol for rabbits can be found in Vaitukaitis, J. et al., J. Clin. Endocrinol. Metab. 33:988-991 (1971).

Booster injections can be given at regular intervals, and antiserum harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, O. et al., Chap. 19 in: Handbook of Experimental Immunology, Wier, D., ed, Blackwell (1973). Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12M). Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D., Chap. 42 in: Manual of Clinical Immunology, second edition, Rose and Friedman, eds., Amer. Soc. For Microbiology, Washington, D.C. (1980)

Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample. In addition, antibodies are useful in various animal models of pneumococcal disease as a means of evaluating the protein used to make the antibody as a potential vaccine target or as a means of evaluating the antibody as a potential immunotherapeutic or immunoprophylactic reagent.

4. Preparation of PCR Primers and Amplification of DNA

Various fragments of the Streptococcus pneumoniae genome, such as those of Tables 1-3 and SEQ ID NOS:1-391 can be used, in accordance with the present invention, to prepare PCR primers for a variety of uses. The PCR primers are preferably at least 15 bases, and more preferably at least 18 bases in length. When selecting a primer sequence, it is preferred that the primer pairs have approximately the same G/C ratio, so that melting temperatures are approximately the same. The PCR primers and amplified DNA of this Example find use in the Examples that follow.

5. Gene expression from DNA Sequences Corresponding to ORFs

A fragment of the Streptococcus pneumoniae genome provided in Tables 1-3 is introduced into an expression vector using conventional technology. Techniques to transfer cloned sequences into expression vectors that direct protein translation in mammalian, yeast, insect or bacterial expression systems are well known in the art. Commercially available vectors and expression systems are available from a variety of suppliers including Stratagene (La Jolla, Calif.), Promega (Madison, Wis.), and Invitrogen (San Diego, Calif.). If desired, to enhance expression and facilitate proper protein folding, the codon context and codon pairing of the sequence may be optimized for the particular expression organism, as explained by Hatfield et al., U.S. Pat. No. 5,082,767, incorporated herein by this reference.

The following is provided as one exemplary method to generate polypeptide(s) from cloned ORFs of the Streptococcus pneumoniae genome fragment. Bacterial ORFs generally lack a poly A addition signal. The addition signal sequence can be added to the construct by, for example, splicing out the poly A addition sequence from pSG5 (Stratagene) using BglI and SalI restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXT1 (Stratagene) for use in eukaryotic expression systems. pXT1 contains the LTRs and a portion of the gag gene of Moloney Murine Leukemia Virus. The positions of the LTRs in the construct allow efficient stable transfection. The vector includes the Herpes Simplex thymidine kinase promoter and the selectable neomycin gene. The Streptococcus pneumoniae DNA is obtained by PCR from the bacterial vector using oligonucleotide primers complementary to the Streptococcus pneumoniae DNA and containing restriction endonuclease sequences for PstI incorporated into the 5′ primer and BglII at the 5′ end of the corresponding Streptococcus pneumoniae DNA 3′ primer, taking care to ensure that the Streptococcus pneumoniae DNA is positioned such that its followed with the poly A addition sequence. The purified fragment obtained from the resulting PCR reaction is digested with PstI, blunt ended with an exonuclease, digested with BglII, purified and ligated to pXT1, now containing a poly A addition sequence and digested BglII.

The ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc., Grand Island, N.Y.) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600 ug/ml G418 (Sigma, St. Louis, Mo.). The protein is preferably released into the supernatant. However if the protein has membrane binding domains, the protein may additionally be retained within the cell or expression may be restricted to the cell surface. Since it may be necessary to purify and locate the transfected product, synthetic 15-mer peptides synthesized from the predicted Streptococcus pneumoniae DNA sequence are injected into mice to generate antibody to the polypeptide encoded by the Streptococcus pneumoniae DNA.

Alternatively and if antibody production is not possible, the Streptococcus pneumoniae DNA sequence is additionally incorporated into eukaryotic expression vectors and expressed as, for example, a globin fusion. Antibody to the globin moiety then is used to purify the chimeric protein. Corresponding protease cleavage sites are engineered between the globin moiety and the polypeptide encoded by the Streptococcus pneumoniae DNA so that the latter may be freed from the formed by simple protease digestion. One useful expression vector for generating globin chimerics is pSG5 (Stratagene). This vector encodes a rabbit globin. Intron TI of the rabbit globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression. These techniques are well known to those skilled in the art of molecular biology. Standard methods are published in methods texts such as Davis et al., cited elsewhere herein, and many of the methods are available from the technical assistance representatives from Stratagene, Life Technologies, Inc., or Promega. Polypeptides of the invention also may be produced using in vitro translation systems such as in vitro Express™ Translation Kit (Stratagene).

While the present invention has been described in some detail for purposes of clarity and understanding, one skilled in the art will appreciate that various changes in form and detail can be made without departing from the true scope of the invention.

All patents, patent applications and publications referred to above are hereby incorporated by reference. TABLE 1 S. pneumoniae - Coding regions containing known sequences Contig ORF Start Stop match percent HSP nt ORF nt ID ID (nt) (nt) acession match gene name ident length length 1 1 437 1003 gb|U41735| Streptococcus pneumoniae peptide methionine 92 200 567 sulfoxide reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 2 5 6169 5720 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase 96 450 450 gene and insertion sequence IS1202 transposase gene, complete cds 2 6 6592 6167 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 98 426 426 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 3 11 9770 9147 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 624 624 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 3 12 10489 9671 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 91 819 819 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 3 13 11546 12019 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 474 474 complete cds, and neuraminidase (nanA) gene, partial cds 3 14 12017 13375 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 1359 1359 complete cds, and neuraminidase (nanA) gene, partial cds 3 15 13421 14338 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 918 918 complete cds, and neuraminidase (nanA) gene, partial cds 3 16 14329 15171 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 843 843 complete cds, and neuraminidase (nanA) gene, partial cds 3 17 15132 17282 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 2151 2151 complete cds, and neuraminidase (nanA) gene, partial cds 3 18 17267 18397 gb|U43526| Streptococcus pneumoniae neuraminidase B (nanB) gene, 99 1069 1131 complete cds, and neuraminidase (nanA) gene, partial cds 4 1 46 1188 emb|Y11463|SPDN Streptococcus pneumoniae dnaG, rpoD, cpoA genes 99 1143 1143 and ORF3 and ORF5 4 2 1198 2529 emb|Y11463|SPDN Streptococcus pneumoniae dnaG, rpoD, cpoA 99 876 1332 genes and ORF3 and ORF5 5 7 11297 11473 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 82 175 177 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 6 7 7125 7364 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence 93 238 240 IS1318 (1372 bp) 6 8 7322 7570 emb|Z77725|SPIS S. pneumoniae DNA for insertion sequence 95 160 249 IS1381 (966 bp) 6 9 7533 7985 emb|Z77725|SPIS S. pneumoniae DNA for insertion 99 453 453 sequence IS1381 (966 bp) 6 23 20197 19733 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 96 465 465 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 7 10 8305 7682 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 95 624 624 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 7 11 9024 8206 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 95 819 819 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 10 13 9304 8078 gb|L29323| Streptococcus pneumoniae methyl transferase 93 513 1227 (mtr) gene cluster, complete cds 11 2 548 919 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 99 316 372 11 3 892 1980 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 99 1089 1089 11 5 3040 3477 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 99 259 438 11 6 3480 3247 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 99 234 234 11 7 3601 4557 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 98 957 957 11 8 4506 4886 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and regR genes 99 381 381 11 9 4884 7142 emb|X16367|SPPB Streptococcus pneumoniae pbpX gene for penicillin 99 2259 2259 binding protein 2X 11 10 7132 8124 emb|X16367|SPPB Streptococcus pneumoniae pbpX gene for 98 70 993 penicillin binding protein 2X 13 1 53 1126 gb|M31296| S. pneumoniae recP gene, complete cds 99 437 1074 14 3 1837 2148 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 87 96 312 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 14 4 2518 2108 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 98 411 411 SAICAR synthetase (purC) genes, complete cds 15 9 8942 8511 gb|U09239| Streptococcus pneumoniae type 19F capsular polysaccharide 89 340 432 biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes, complete cds, and aliA gene, partial cds 17 7 3910 3458 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 98 453 453 17 8 4304 3873 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 96 382 432 19 1 41 529 emb|X94909|SPIG S. pneumoniae iga gene 75 368 489 19 2 554 757 gb|L07752| Streptococcus pneumoniae attachment site (attB), DNA sequence 99 167 204 19 3 946 1827 gb|L07752| Streptococcus pneumoniae attachment site (attB), DNA sequence 94 100 882 20 1 937 182 gb|U33315| Streptococcus pneumoniae orfL gene, partial cds, competence 99 756 756 stimulating peptide precursor (comC), histidine protein kinase (comD) and response regulator (comE) genes, complete cds, tRNA-Arg and tRNA-Gln genes 20 2 2271 931 gb|U33315| Streptococcus pneumoniae orfL gene, partial cds, 98 1341 1341 competence stimulating peptide precursor (comC), histidine protein kinase (comD) and response regulator (comE) genes, complete cds, tRNA-Arg and tRNA-Gln genes 20 3 3175 2684 gb|U76218| Streptococcus pneumoniae competence stimulating peptide 99 492 492 precursor ComC (comC), histidine kinase homolog ComD (comD), and response regulator homolog ComE (comE) genes, complete cds 20 4 3322 4527 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 99 1206 1206 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 20 5 4573 5343 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 99 771 771 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 20 6 5532 6917 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 99 1386 1386 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 20 7 6995 8212 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 99 1218 1218 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 20 8 8214 8471 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 98 258 258 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 20 9 8534 9670 gb|AF000658| Streptococcus pneumoniae R801 tRNA-Arg gene, partial 99 134 1137 sequence, and putative serine protease (sphtra), SPSpoJ (spspoJ), initiator protein (spdnaa) and beta subunit of DNA polymerase III (spdnan) genes, complete cds 22 14 11887 12267 emb|Z77726|SP1S S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 99 226 381 22 15 12708 12256 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 97 353 453 22 16 13165 12662 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 98 504 504 22 23 18398 18910 emb|Z86112|SPZ8 S. pneumoniae genes encoding galacturonosyl 95 463 513 transferase and transposase and insertion sequence IS1515 22 24 18829 19299 emb|Z86112|SPZ8 S. pneumoniae genes encoding galacturonosyl 99 443 471 transferase and transposase and insertion sequence IS1515 23 5 5624 4203 emb|X52474|SPPL S. pneumoniae ply gene for pneumolysin 99 1422 1422 23 6 6063 5629 gb|M17717| S. pneumoniae pneumolysin gene, complete cds 98 197 435 26 1 5500 2 emb|X94909|SPIG S. pneumoniae iga gene 87 3487 5499 26 2 5823 5584 gb|U47687| Streptococcus pneumoniae immunoglobulin A1 99 151 240 protease (iga) gene, complete cds 26 3 6878 5685 gb|U47687| Streptococcus pneumoniae immunoglobulin A1 100 50 1194 protease (iga) gene, complete cds 26 8 14498 14854 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 99 338 357 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 26 9 14763 14924 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 100 94 162 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 26 10 14922 15173 gb|U04047| Streptococcus pneumoniae SSZ dextran 97 242 252 glucosidase gene and insertion sequence IS1202 transposase gene, complete cds 28 1 80 505 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 99 426 426 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 28 2 503 952 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene and 97 450 450 insertion sequence IS1202 transposase gene, complete cds 28 3 780 1298 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene and 96 181 519 insertion sequence IS1202 transposase gene, complete cds 34 1 207 1523 gb|L08611| Streptococcus pneumoniae maltose/maltodextrin uptake 99 1317 1317 (malX) and two maltodextrin permease (malC and malD) genes, complete cds 34 2 1477 2367 gb|L08611| Streptococcus pneumoniae maltose/maltodextrin 96 795 891 uptake (malX) and two maltodextrin permease (malC and malD) genes, complete cds 34 3 2593 3420 gb|L21856| Streptococcus pneumoniae malA gene, complete cds; 96 446 828 malR gene, complete cds 34 4 2790 2647 gb|L21856| Streptococcus pneumoniae malA gene, complete cds; 98 137 144 malR gene, complete cds 34 5 3418 4416 gb|L21856| Streptococcus pneumoniae malA gene, complete cds; 96 999 999 malR gene, complete cds 34 9 7764 7507 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 93 201 258 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 34 16 10562 10257 emb|X63602|SPBO S. pneumoniae mmsA-Box 92 238 306 35 4 1176 1439 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 87 248 264 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 35 5 1458 1961 gb|U09239| Streptococcus pneumoniae type 19F capsular 98 264 504 polysaccharide biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes, complete cds, and aliA gene, partial cds 35 17 16172 15477 emb|X85787|SPCP S. pneumoniae dexB, cps14A, cps14B, cps14C, cps14D, 97 696 696 cps14E, cps14F, cps14G, cps14H, cps14I, cps14J, cps14K, cps14L, tasA genes 35 18 16961 16170 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 86 792 792 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 35 19 17620 16871 gb|U09239| Streptococcus pneumoniae type 19F capsular 83 750 750 polysaccharide biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes, complete cds, and aliA gene, partial cds 35 20 19061 17604 emb|X85787|SPCP S. pneumoniae dexB, cps14A, cps14B, 94 1458 1458 cps14C, cps14D, cps14E, cps14F, cps14G, cps14H, cps14I, cps14J, cps14K, cps14L, tasA genes 36 19 18960 18352 gb|U40786| Streptococcus pneumoniae surface antigen A variant 99 609 609 precursor (psaA) and 18 kDa protein genes, complete cds, and ORF1 gene, partial cds 36 20 19934 18966 gb|U53509| Streptococcus pneumoniae surface adhesin A 99 969 969 precursor (psaA) gene, complete cds 37 1 2743 179 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase 99 2565 2565 genes and unknown orf 37 2 2985 2824 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase 100 162 162 genes and unknown orf 37 3 5034 3070 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase 99 1965 1965 genes and unknown orf 37 4 5134 5790 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase 99 657 657 genes and unknown orf 37 5 6171 5833 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase 96 339 339 genes and unknown orf 38 19 12969 13268 gb|M28679| S. pneumoniae promoter region DNA 100 64 300 39 2 1256 2137 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 99 882 882 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 39 3 2405 3370 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 99 966 966 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 40 9 5253 7208 gb|M29686| S. pneumoniae mismatch repair (hexB) gene, complete cds 99 1956 1956 41 1 3 1037 emb|Z17307|SPRE S. pneumoniae recA gene encoding RecA 99 1027 1035 41 2 1328 2713 emb|Z34303|SPCI Streptococcus pneumoniae cin operon encoding 99 1386 1386 the cinA, recA, dinF, lytA genes, and downstream sequences 41 3 3083 4045 gb|M13812| S. pneumoniae autolysin (lytA) gene, complete cds 99 963 963 41 4 3272 3096 gb|M13812| S. pneumoniae autolysin (lytA) gene, complete cds 100 177 177 41 5 3603 3860 gb|M13812| S. pneumoniae autolysin (lytA) gene, complete cds 100 258 258 41 6 4755 5162 gb|L36660| Streptococcus pneumoniae ORF, complete cds 98 408 408 41 7 5270 5716 gb|L36660| Streptococcus pneumoniae ORF, complete cds 98 447 447 41 8 6112 6918 gb|L36660| Streptococcus pneumoniae ORF, complete cds 98 431 807 41 9 6916 7119 gb|L36660| Streptococcus pneumoniae ORF, complete cds 100 204 204 41 10 7082 7660 gb|L36660| Streptococcus pneumoniae ORF, complete cds 97 552 579 41 11 7680 7979 gb|L36660| Streptococcus pneumoniae ORF, complete cds 98 81 300 41 12 9169 8717 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 97 353 453 41 13 9533 9132 emb|Z77725|SPIS S. pneumoniae DNA for insertion sequence IS1381 (966 bp) 95 160 402 41 14 9669 9475 emb|Z82001|SPZ8 S. pneumoniae pcpA gene and open reading frames 100 189 195 44 5 7190 7555 emb|Z82001|SPZ8 S. pneumoniae pcpA gene and open reading frames 99 366 366 44 6 8059 7607 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 97 453 453 44 7 8423 8022 emb|Z77725|SPIS S. pneumoniae DNA for insertion sequence IS1381 (966 bp) 95 160 402 44 8 8559 8365 emb|Z82001|SPZ8 S. pneumoniae pcpA gene and open reading frames 100 189 195 48 9 6480 4687 gb|L39074| Streptococcus pneumoniae pyruvate oxidase (spxB) 99 1794 1764 gene, complete cds 49 2 231 2603 gb|L20561| Streptococcus pneumoniae Exp7 gene, partial cds 100 216 2373 53 6 2407 2156 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene 97 242 252 and insertion sequence IS1202 transposase gene, complete cds 53 7 2566 2405 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 100 94 162 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 53 8 2831 2475 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 99 338 357 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 54 13 12409 11105 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 67 591 1305 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 55 22 20488 19949 emb|Z84379|HSZ8 S. pneumoniae dfr gene (isolate 92) 99 540 540 61 11 11864 9900 emb|Z16082|PNAL Streptococcus pneumoniae aliB gene 98 1965 1965 63 1 3 239 gb|M18729| S. pneumoniae mismatch repair protein (hexA) 100 237 237 gene, complete cds 63 2 233 2611 gb|M18729| S. pneumoniae mismatch repair protein (hexA) 99 2330 2379 gene, complete cds 63 3 2557 2823 gb|M18729| S. pneumoniae mismatch repair protein (hexA) gene, 99 266 267 complete cds 63 4 2958 4664 gb|M18729| S. pneumoniae mismatch repair protein (hexA) gene, 95 69 1707 complete cds 67 6 3770 3399 gb|L20670| Streptococcus pneumoniae hyaluronidase gene, complete cds 96 372 372 67 7 7161 4171 gb|L20670| Streptococcus pneumoniae hyaluronidase gene, complete cds 99 2938 2991 70 1 1 702 gb|M14340| S. pneumoniae DpnI gene region encoding dpnC and dpnD, 100 693 702 complete cds 70 2 678 1160 gb|M14340| S. pneumoniae DpnI gene region encoding dpnC 100 483 483 and dpnD, complete cds 70 3 2490 1210 gb|M14339| S. pneumoniae DpnII gene region encoding dpnM, 98 462 1281 dpnA, dpnB, complete cds 70 7 4230 4424 gb|J04234| S. pneumoniae exodeoxyribonuclease (exoA) gene, complete cds 99 147 195 70 8 5197 4316 gb|J04234| S. pneumoniae exodeoxyribonuclease (exoA) gene, complete cds 99 881 882 70 13 8108 9874 gb|L20562| Streptococcus pneumoniae Exp8 gene, partial cds 93 234 1767 71 22 27964 28341 emb|X62602|SPBO S. pneumoniae mmsA-Box 93 233 378 72 5 4607 3552 emb|Z26850|SPAT S. pneumoniae (M222) genes for ATPase a 97 102 1056 subunit, ATPase b subunit and ATPase c subunit 73 1 471 133 emb|X63602|SPBO S. pneumoniae mmsA-Box 91 193 339 73 3 3658 977 gb|J04479| S. pneumoniae DNA polymerase I (polA) gene, complete cds 99 2682 2682 73 8 4864 5379 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 98 318 516 SAICAR synthetase (purC) genes, complete cds 77 3 2622 1999 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 95 624 624 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 77 4 3341 2523 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 91 819 819 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 78 1 341 3 emb|X77249|SPR6 S. pneumoniae (R6) ciaR/ciaH genes 99 339 339 78 2 1095 325 emb|X77249|SPR6 S. pneumoniae (R6) ciaR/ciaH genes 99 771 771 82 10 11436 10816 gb|U90721| Streptococcus pneumoniae signal peptidase I (spi) gene, 97 621 621 complete cds 82 11 12402 11434 gb|U93576| Streptococcus pneumoniae ribonuclease HII (rnhB) gene, 98 953 969 complete cds 82 12 12381 12704 gb|U93576| Streptococcus pneumoniae ribonuclease HII (rnhB) gene, 100 51 324 complete cds 83 8 3212 3550 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 97 290 339 83 10 4662 6851 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) 99 2190 2190 and SAICAR synthetase (purC) genes, complete cds 83 11 6849 8213 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) 99 1365 1365 and SAICAR synthetase (purC) genes, complete cds 83 12 8236 9090 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) 99 855 855 and SAICAR synthetase (purC) genes, complete cds 83 13 9283 13017 gb|L15190| Streptococcus pneumoniae SAICAR synthetase (purC) gene, 100 107 3735 complete cds 83 23 22147 23313 gb|L36923| Streptococcus pneumoniae beta-N-acetylhexosaminidase 98 218 1167 (strH) gene, complete cds 83 24 23268 23450 gb|L36923| Streptococcus pneumoniae beta-N-acetylhexosaminidase 98 172 183 (strH) gene, complete cds 83 25 27527 23505 gb|L36923| Streptococcus pneumoniae beta-N-acetylhexosaminidase 99 3826 4023 (strH) gene, complete cds 83 26 28472 27771 gb|L36923| Streptococcus pneumoniae beta-N-acetylhexosaminidase 99 416 702 (strH) gene, complete cds 84 4 4554 6173 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 98 697 1620 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 87 6 5951 5316 emb|Z77725|SPIS S. pneumoniae DNA for insertion sequence IS1381 (966 bp) 96 439 636 88 5 2957 3511 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 94 555 555 SAICAR synthetase (purC) genes, complete cds 88 6 3466 4269 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 94 804 804 SAICAR synthetase (purC) genes, complete cds 89 13 9878 10093 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 97 211 216 SAICAR synthetase (purC) genes, complete cds 89 14 10062 10412 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 97 335 351 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 93 10 5303 4941 emb|X63602|SPBO S. pneumoniae mmsA-Box 89 237 363 97 4 1708 1520 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 91 140 189 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 99 1 89 700 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 93 592 612 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 99 2 1773 775 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 99 998 999 resistance 99 3 2794 1712 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 99 1083 1083 resistance 99 4 3732 2788 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 100 945 945 resistance 99 5 5249 3714 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 100 1536 1536 resistance 99 6 7262 5277 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 99 1986 1986 resistance 101 1 216 1538 emb|X54225|SPEN S. pneumoniae epuA and endA genes for 7 kDa protein and 99 146 1323 membrane endonuclease 101 2 1492 1719 emb|X54225|SPEN S. pneumoniae epuA and endA genes for 7 kDa protein and 99 228 228 membrane endonuclease 101 3 1694 1855 emb|X54225|SPEN S. pneumoniae epuA and endA genes for 7 kDa protein and 100 162 162 membrane endonuclease 101 4 1701 2582 emb|X54225|SPEN S. pneumoniae epuA and endA genes for 7 kDa protein and 100 882 882 membrane endonuclease 103 7 5556 5041 emb|Z95914|SPEN Streptococcus pneumoniae sodA gene 100 396 516 104 2 1347 1556 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 83 206 210 105 5 5381 5028 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 98 353 354 unknown orf 105 6 6089 5379 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 98 84 711 unknown orf 107 4 2785 1880 emb|X16022|SPPE S. pneumoniae penA gene 98 72 906 107 5 2913 4988 emb|X16022|SPPE S. pneumoniae penA gene 99 1692 2076 107 6 4981 5595 emb|X13136|SPPE Streptococcus pneumoniae penA gene for penicillin 91 107 615 binding protein 2B lacking N-term. (penicillin resistant strain) 108 9 9068 8718 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 95 342 351 unknown orf 108 12 11308 10922 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 99 199 387 unknown orf 109 3 2768 2241 emb|Z77725|SPIS S. pneumoniae DNA for insertion sequence IS1381 (966 bp) 96 61 528 109 4 2688 2855 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 96 148 168 109 5 2862 3269 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 97 353 408 109 6 5320 3584 gb|M18729| S. pneumoniae mismatch repair protein (hexA) gene, 100 371 1737 complete cds 113 1 431 3 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 95 429 429 SAICAR synthetase (purC) genes, complete cds 113 10 9788 8532 emb|X99400|SPDA S. pneumoniae dacA gene and ORF 99 1257 1257 113 11 9870 10985 emb|X99400|SPDA S. pneumoniae dacA gene and ORF 99 1116 1116 114 3 2530 2030 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 95 481 501 SAICAR synthetase (purC) genes, complete cds 115 11 11303 10932 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene 97 372 372 and insertion sequence IS1202 transposase gene, complete cds 117 1 897 3302 emb|X72967|SPNA S. pneumoniae nanA gene 99 2402 2406 117 2 3277 3831 emb|X72967|SPNA S. pneumoniae nanA gene 99 237 555 117 3 4327 3899 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 98 429 429 SAICAR synthetase (purC) genes, complete cds 121 2 1369 1941 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 99 202 573 gene, complete cds and DnaJ (dnaJ) gene, partial cds 121 3 2412 4253 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 99 1842 1842 gene, complete cds and DnaJ (dnaJ) gene, partial cds 122 8 5066 5587 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene 64 451 522 and insertion sequence IS1202 transposase gene, complete cds 125 1 1811 189 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 92 99 1623 SAICAR synthetase (purC) genes, complete cds 128 15 12496 11204 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 91 705 1293 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 134 1 1 492 emb|Y10818|SPY1 S. pneumoniae spsA gene 99 203 492 134 2 556 2652 gb|AF019904| Streptococcus pneumoniae choline binding protein A (cbpA) 86 685 2097 gene, partial cds 134 3 1160 837 emb|Y10818|SPY1 S. pneumoniae spsA gene 86 324 324 134 4 3952 2882 gb|AF019904| Streptococcus pneumoniae choline binding protein A (cbpA) 98 215 1071 gene, partial cds 134 8 7992 9848 gb|U12567| Streptococcus pneumoniae P13 glycerol-3-phosphate 99 285 1857 dehydrogenase (glpD) gene, partial cds, and glycerol uptake facilitator (glpF) and ORF3 genes, complete cds 134 9 9846 10622 gb|U12567| Streptococcus pneumoniae P13 glycerol-3-phosphate 99 570 777 dehydrogenase (glpD) gene, partial cds, and glycerol uptake facilitator (glpF) and ORF3 genes, complete cds 134 10 10805 11122 gb|U12567| Streptococcus pneumoniae P13 glycerol-3-phosphate 100 318 318 dehydrogenase (glpD) gene, partial cds, and glycerol uptake facilitator (glpF) and ORF3 genes, complete cds 137 13 7970 8443 gb|U09239| Streptococcus pneumoniae type 19F capsular 90 420 474 polysaccharide biosynthesis operon, (cps19fABCDEFGHIJKLMNO) genes, complete cds, and aliA gene, partial cds 137 14 8590 8775 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 174 186 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 137 15 8773 8967 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 98 195 195 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 137 16 9223 9687 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence IS1318 (1372 bp) 96 446 465 137 17 9641 10051 emb|Z77727|SPIS S. pneumoniae DNA for insertion sequence IS1318 (823 bp) 96 293 411 139 10 12998 12702 emb|X63602|SPBO S. pneumoniae mmsA-Box 90 234 297 141 8 7805 8938 emb|Z49988|SPMM Streptococcus pneumoniae mmsA gene 99 338 1134 141 9 8936 10972 emb|Z49988|SPMM Streptococcus pneumoniae mmsA gene 99 2037 2037 141 10 11472 12467 emb|Z49988|SPMM Streptococcus pneumoniae mmsA gene 100 76 996 142 2 257 814 gb|M80215| Streptococcus pneumoniae uvs402 protein gene, 98 174 558 complete cds 142 3 787 957 gb|M80215| Streptococcus pneumoniae uvs402 protein gene, 100 142 171 complete cds 142 4 980 3022 gb|M80215| Streptococcus pneumoniae uvs402 protein gene, 95 1997 2043 complete cds 142 5 3020 3595 gb|M80215| Streptococcus pneumoniae uvs402 protein gene, 100 153 576 complete cds 145 1 1 219 emb|Z35135|SPAL S. pneumoniae aliA gene for amiA-like gene A 97 185 219 145 2 171 1994 gb|L20556| Streptococcus pneumoniae plpA gene, partial cds 99 1811 1824 145 3 2287 7599 emb|Z47210|SPDE S. pneumoniae dexB, cap3A, cap3B and cap3C genes and orfs 99 1052 5313 145 4 9934 7766 gb|M90527| Streptococcus pneumoniae penicillin-binding protein (ponA) 99 2169 2169 gene, complete cds 145 5 10488 9922 gb|M90527| Streptococcus pneumoniae penicillin-binding protein (ponA) 99 512 567 gene, complete cds 146 1 159 4 emb|Z82002|SPZ8 S. pneumoniae pcpB and pcpC genes 98 156 156 146 2 344 90 emb|Z82002|SPZ8 S. pneumoniae pcpB and pcpC genes 98 255 255 146 16 11795 10794 emb|Z82002|SPZ8 S. pneumoniae pcpB and pcpC genes 85 276 1002 147 11 10678 10202 emb|Z21702|SPUN S. pneumoniae ung gene and mutX genes encoding 98 477 477 uracil-DNA glycosylase and 8-oxodGTP nucleoside triphosphatase 147 12 11338 10676 emb|Z21702|SPUN S. pneumoniae ung gene and mutX genes encoding 99 663 663 uracil-DNA glycosylase and 8-oxodGTP nucleoside triphosphatase 148 12 9009 8815 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 90 180 195 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 156 4 1154 1402 emb|X63602|SPBO S. pneumoniae mmsA-Box 94 185 249 159 13 9048 8521 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) 98 526 528 and SAICAR synthetase (purC) genes, complete cds 160 1 1 147 emb|Z26851|SPAT S. pneumoniae (R6) genes for ATPase a subunit, 100 142 147 ATPase b subunit and ATPase c subunit 160 2 179 898 emb|Z26851|SPAT S. pneumoniae (R6) genes for ATPase a subunit, 99 720 720 ATPase b subunit and ATPase c subunit 160 3 906 1406 emb|Z26850|SPAT S. pneumoniae (M222) genes for ATPase a subunit, 95 501 501 ATPase b subunit and ATPase c subunit 160 4 1373 1942 emb|Z26850|SPAT S. pneumoniae (M222) genes for ATPase a subunit, 87 306 570 ATPase b subunit and ATPase c subunit 161 1 1 984 emb|X77249|SPR6 S. pneumoniae (R6) ciaR/ciaH genes 99 984 984 161 7 6910 7497 emb|X83917|SPGY S. pneumoniae orflgyrB and gyrB gene encoding DNA 99 437 588 gyrase B subunit 161 8 7443 9386 emb|X83917|SPGY S. pneumoniae orflgyrB and gyrB gene encoding DNA 98 1912 1944 gyrase B subunit 163 1 2 2155 gb|L20559| Streptococcus pneumoniae Exp5 gene, partial cds 98 327 2154 165 1 32 1618 gb|J01796| S. pneumoniae malX and malM genes encoding membrane 99 1587 1587 protein and amylomaltase, complete cds, and malP gene encoding phosphorylase 165 2 1608 3902 gb|J01796| S. pneumoniae malX and malM genes encoding membrane 100 280 2295 protein and amylomaltase, complete cds, and malP gene encoding phosphorylase 166 1 378 4 emb|Y11463|SPDN Streptococcus pneumoniae dnaG, rpoD, cpoA genes and 100 375 375 ORF3 and ORF5 166 2 1507 320 emb|Y11463|SPDN Streptococcus pneumoniae dnaG, rpoD, cpoA genes and 99 1188 1188 ORF3 and ORF5 166 3 3240 1432 emb|Y11463|SPDN Streptococcus pneumoniae dnaG, rpoD, cpoA genes and 99 563 1809 ORF3 and ORF5 167 1 1077 328 emb|Z71552|SPAD Streptococcus pneumoniae adcCBA operon 94 155 750 167 2 1844 999 emb|Z71552|SPAD Streptococcus pneumoniae adcCBA operon 98 405 846 167 3 2714 1842 emb|Z71552|SPAD Streptococcus pneumoniae adcCBA operon 97 604 873 167 4 3399 2641 emb|Z71552|SPAD Streptococcus pneumoniae adcCBA operon 99 703 759 168 1 1 2259 gb|L20558| Streptococcus pneumoniae Exp4 gene, partial cds 99 282 2259 170 10 7338 7685 emb|Z77726|SPIS S. pneumoniae DNA for insertion sequence 95 315 348 IS1318 (1372 bp) 172 6 2462 4981 gb|U47625| Streptococcus pneumoniae formate acetyltransferase 97 365 2520 (exp72) gene, partial cds 175 1 373 20 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 89 353 354 SAICAR synthetase (purC) genes, complete cds 175 4 1843 3621 emb|Z47210|SPDE S. pneumoniae dexB, cap3A, cap3B and cap3C genes 95 89 1779 and orfs 176 5 3984 2980 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 100 573 1005 unknown orf 178 1 3 425 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 95 423 423 unknown orf 179 1 426 70 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 99 338 357 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 180 3 3084 1855 emb|X95718|SPGY S. pneumoniae gyrA gene 99 381 1230 186 1 714 4 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and 98 59 711 regR genes 186 2 2254 608 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX and 98 315 1647 regR genes 186 3 707 880 emb|Z79691|SOOR S. pneumoniae yorf[A, B, C, D, E], ftsL, pbpX 98 174 174 and regR genes 189 1 2 259 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 99 258 258 gene, complete cds and DnaJ (dnaJ) gene, partial cds 189 2 600 385 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 98 204 216 gene, complete cds and DnaJ (dnaJ) gene, partial cds 189 3 1018 851 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 99 168 168 gene, complete cds and DnaJ (dnaJ) gene, partial cds 189 4 1012 2154 gb|U72720| Streptococcus pneumoniae heat shock protein 70 (dnaK) 99 1062 1143 gene, complete cds and DnaJ (dnaJ) gene, partial cds 191 9 7829 7524 emb|X63602|SPBO S. pneumoniae mmsA-Box 95 234 306 194 1 1 729 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 91 728 729 SAICAR synthetase (purC) genes, complete cds 199 2 1117 881 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 96 211 237 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 199 4 1499 1762 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 89 248 264 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 199 5 1781 2284 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 98 504 504 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 203 1 1977 337 gb|L20563| Streptococcus pneumoniae Exp9 gene, partial cds 99 342 1641 204 1 1145 3 gb|L36131| Streptococcus pneumoniae exp10 gene, complete cds, recA 99 1143 1143 gene, 5′ end 208 1 59 2296 gb|U89711| Streptococcus pneumoniae pneumococcal surface protein 90 471 2238 A PspA (pspA) gene, complete cds 213 3 2455 2123 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 96 332 333 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 216 1 368 12 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 99 338 357 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 216 3 2650 2327 gb|M28678| S. pneumoniae promoter sequence DNA 98 86 324 222 1 417 4 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 414 414 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 227 3 5266 4238 emb|AJ000336|SP Streptococcus pneumoniae ldh gene 99 1029 1029 239 1 1 804 gb|M31296| S. pneumoniae recP gene, complete cds 95 484 804 247 3 1625 1807 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 94 178 183 SAICAR synthetase (purC) genes, complete cds 249 3 921 1364 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 443 444 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 253 1 362 3 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 99 360 360 SAICAR synthetase (purC) genes, complete cds 253 5 1238 2050 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 95 420 813 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 253 6 2069 2572 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 97 504 504 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 255 1 3 800 emb|Z82002|SPZ8 S. pneumoniae pcpB and pcpC genes 97 531 798 255 2 798 1841 emb|Z82002|SPZ8 S. pneumoniae pcpB and pcpC genes 97 672 1044 255 3 2493 1969 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes 92 435 525 and unknown orf 257 2 985 770 emb|X17337|SPAM Streptococcus pneumoniae ami locus conferring aminopterin 96 117 216 resistance 257 3 1245 907 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) and 97 339 339 SAICAR synthetase (purC) genes, complete cds 267 2 495 1208 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 95 84 714 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 267 3 1291 2277 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 97 755 987 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 267 4 2261 3601 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 98 1341 1341 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 267 5 3561 4136 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 99 576 576 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 267 6 4164 4949 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 99 748 786 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 267 7 5544 5140 gb|U16156| Streptococcus pneumoniae dihydropteroate synthase (sulA), 100 186 405 dihydrofolate synthetase (sulB), guanosine triphosphate cyclohydrolase (sulC), aldolase-pyrophosphokinase (sulD) genes, complete cds 268 4 1793 1990 emb|X63602|SPBO S. pneumoniae mmsA-Box 89 194 198 271 1 562 104 gb|M29686| S. pneumoniae mismatch repair (hexB) gene, complete cds 93 160 459 291 1 75 524 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene 96 450 450 and insertion sequence IS1202 transposase gene, complete cds 291 2 1001 525 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 87 205 477 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 291 3 807 559 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 90 170 249 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 291 4 1374 1099 gb|M36180| Streptococcus pneumoniae transposase, (comA and comB) 85 264 276 and SAICAR synthetase (purC) genes, complete cds 293 1 3 1673 emb|Z67740|SPGY S. pneumoniae gyrB gene and unknown orf 98 553 1671 296 1 1434 151 emb|Z47210|SPDE S. pneumoniae dexB, cap3A, cap3B and cap3C genes and orfs 99 430 1284 317 1 157 510 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes and 89 353 354 unknown orf 325 2 1237 485 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 91 299 753 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 326 1 1 462 emb|Z82001|SPZ8 S. pneumoniae pcpA gene and open reading frames 100 233 462 327 1 603 64 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 89 540 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 334 1 153 545 gb|U41735| Streptococcus pneumoniae peptide methionine sulfoxide 87 91 393 reductase (msrA) and homoserine kinase homolog (thrB) genes, complete cds 336 1 308 93 emb|Z26850|SPAT S. pneumoniae (M222) genes for ATPase a subunit, 97 102 216 ATPase b subunit and ATPase c subunit 360 1 1 519 emb|Z67739|SPPA S. pneumoniae parC, parE and transposase genes 95 435 519 and unknown orf 360 4 1598 1960 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 94 353 363 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 362 1 673 2 emb|Z83335|SPZ8 S. pneumoniae dexB, cap1[A, B, C, D, E, F, G, H, I, J, 95 63 672 K] genes, dTDP-rhamnose biosynthesis genes and aliA gene 362 2 1168 728 gb|U04047| Streptococcus pneumoniae SSZ dextran glucosidase gene and 96 441 441 insertion sequence IS1202 transposase gene, complete cds 384 1 347 111 emb|X85787|SPCP S. pneumoniae dexB, cps14A, cps14B, cps14C, 94 54 237 cps14D, cps14E, cps14F, cps14G, cps14H, cps14I, cps14J, cps14K, cps14L, tasA genes

TABLE 2 S. pneumoniae - Putative coding regions of novel proteins similar to known proteins Contig ORF Start Stop match length ID ID (nt) (nt) acession match gene name % sim % ident (nt) 228 2 1760 1942 pir|F60663|F606 translation elongation factor Tu - Streptococcus oralis 100 100 183 319 1 2 205 gi|984927 neomycin phosphotransferase [Cloning vector pBSL99] 100 100 204 260 1 2 1138 pir|F60663|F606 translation elongation factor Tu - Streptococcus oralis 99 98 1137 25 2 486 1394 gi|1574495 hypothetical [Haemophilus influenzae] 98 96 909 94 2 685 1002 gi|310627 phosphoenolpyruvate:sugar phosphotransferase system 98 93 318 HPr [Streptococcus mutans] 312 1 190 2 gi|347999 ATP-dependent protease proteolytic 98 95 189 subunit [Streptococcus salivarius] 329 1 1 807 gi|924848 inosine monophosphate dehydrogenase [Streptococcus pyogenes] 98 94 807 336 2 290 589 gi|987050 lacZ gene product [unidentified cloning vector] 98 98 300 181 9 5948 7366 gi|153755 phospho-beta-D-galactosidase (EC 3.2.1.85) 97 94 1419 [Lactococcus lactis cremoris] 312 2 1044 361 gi|347998 uracil phosphoribosyltransferase [Streptococcus salivarius] 97 88 684 32 8 6575 7486 sp|P37214|ERA_S GTP-BINDING PROTEIN ERA HOMOLOG. 96 91 912 94 3 951 2741 gi|153615 phosphoenolpyruvate:sugar phosphotransferase system enzyme 96 92 1791 I [Streptococcus salivarius] 127 1 1 168 gi|581299 initiation factor IF-1 [Lactococcus lactis] 96 89 168 128 14 10438 11154 gi|1276873 DeoD [Streptococcus thermophilus] 96 93 717 181 4 1362 1598 gi|46606 lacD polypeptide (AA 1-326) [Staphylococcus aureus] 96 80 237 218 1 1 834 gi|1743856 intrageneric coaggregation-relevant adhesin 96 93 834 [Streptococcus gordonii] 319 2 115 441 gi|208225 heat-shock protein 82/neomcyn phosphotransferase fusion 96 96 327 protein (hsp82-neo) [unidentified cloning vector] 54 12 8622 10967 gnl|PID|d100972 Pyruvate formate-lyase [Streptococcus mutans] 95 89 2346 181 2 606 1289 gi|149396 lacD [Lactococcus lactis] 95 89 684 46 3 3410 3045 gi|1850606 YlxM [Streptococcus mutans] 94 86 366 89 10 7972 7337 gi|703442 thymidine kinase [Streptococcus gordonii] 94 86 636 148 9 6431 7354 gi|995767 UDP-glucose pyrophosphorylase [Streptococcus pyogenes] 94 85 924 160 7 4430 5848 gi|153573 H+ ATPase [Enterococcus faecalis] 94 87 1419 2 3 4598 3513 gi|153763 plasmin receptor [Streptococcus pyogenes] 93 86 1086 12 8 7877 6204 gi|1103865 formyl-tetrahydrofolate synthetase [Streptococcus mutans] 93 84 1674 65 11 4734 5120 gi|40150 L14 protein (AA 1-122) [Bacillus subtilis] 93 87 387 68 1 53 1297 gi|47341 antitumor protein [Streptococcus pyogenes] 93 87 1245 80 1 3 299 gnl|PID|d101166 ribosomal protein S7 [Bacillus subtilis] 93 84 297 127 3 695 1093 gi|142462 ribosomal protein S11 [Bacillus subtilis] 93 86 399 160 5 1924 3462 gi|1773264 ATPase, alpha subunit [Streptococcus mutans] 93 85 1539 211 5 3757 3047 gi|535273 aminopeptidase C [Streptococcus thermophilus] 93 82 711 262 1 16 564 gi|149394 lacB [Lactococcus lactis] 93 90 549 366 1 197 3 gi|295259 tryptophan synthase beta subunit [Synechocystis sp.] 93 91 195 25 3 1392 1976 gi|1574496 hypothetical [Haemophilus influenzae] 92 80 585 36 21 20781 19927 gi|310632 hydrophobic membrane protein [Streptococcus gordonii] 92 86 855 181 3 1265 1534 gi|149396 lacD [Lactococcus lactis] 92 83 270 181 7 3662 4060 gi|149410 enzyme III [Lactococcus lactis] 92 83 399 32 4 5631 3937 gnl|PID|e294090 fibronectin-binding protein-like protein A 91 85 1695 [Streptococcus gordonii] 46 2 3054 1462 gi|1850607 signal recognition particle Ffh [Streptococcus mutans] 91 84 1593 65 10 4442 4726 pir|S17865|S178 ribosomal protein S17 - Bacillus stearothermophilus 91 80 285 77 2 260 1900 gi|287871 groEL gene product [Lactococcus lactis] 91 82 1641 84 1 2 2056 gi|871784 Clp-like ATP-dependent protease binding subunit [Bos taurus] 91 79 2055 99 8 10750 9272 gi|153740 sucrose phosphorylase [Streptococcus mutans] 91 84 1479 99 9 11947 11072 gi|153739 membrane protein [Streptococcus mutans] 91 78 876 127 5 2065 2469 pir|S07223|R5BS ribosomal protein L17 - Bacillus stearothermophilus 91 78 405 132 6 9539 9390 gi|143065 hubst [Bacillus stearothermophilus] 91 89 150 137 8 4765 6153 gnl|PID|d100347 Na+-ATPase beta subunit [Enterococcus hirae] 91 79 1389 151 7 11119 9734 gi|1815634 glutamine synthetase type 1 [Streptococcus agalactiae] 91 82 1386 201 2 1798 278 gi|2208998 dextran glucosidase DexS [Streptococcus suis] 91 79 1521 222 2 673 1839 gi|153741 ATP-binding protein [Streptococcus mutans] 91 85 1167 293 5 4113 4400 gi|1196921 unknown protein [Insertion sequence IS861] 91 71 288 32 7 6166 6570 pir|A36933|A369 diacylglycerol kinase homolog - Streptococcus mutans 90 77 405 33 2 841 527 gi|1196921 unknown protein [Insertion sequence IS861] 90 70 315 48 27 20908 19757 gnl|PID|e274705 lactate oxidase [Streptococcus iniae] 90 80 1152 55 21 19777 18515 gnl|PID|e221213 ClpX protein [Bacillus subtilis] 90 75 1263 56 2 717 977 gi|1710133 flagellar filament cap [Borrelia burgdorferi] 90 50 261 65 1 1 606 gi|1165303 L3 [Bacillus subtilis] 90 75 606 114 1 2 988 gi|153562 aspartate beta-semialdehyde dehydrogenase 90 80 987 (EC 1.2.1.11) [Streptococcus mutans] 120 1 1345 827 gi|407880 ORF1 [Streptococcus equisimilis] 90 75 519 159 12 7690 8298 gi|143012 GMP synthetase [Bacillus subtilis] 90 84 609 166 4 4076 3282 gi|1661179 high affinity branched chain amino acid transport 90 78 795 protein [Streptococcus mutans] 183 1 28 1395 gi|308858 ATP:pyruvate 2-O-phosphotransferase [Lactococcus lactis] 90 76 1368 191 3 2891 1662 gi|149521 tryptophan synthase beta subunit [Lactococcus lactis] 90 78 1230 198 2 1551 436 gi|2323342 (AF014460) CcpA [Streptococcus mutans] 90 76 1116 305 1 37 783 gi|1573551 asparagine synthetase A (asnA) [Haemophilus influenzae] 90 80 747 8 3 2285 3343 gi|149434 putative [Lactococcus lactis] 89 78 1059 46 8 7577 7362 pir|A45434|A454 ribosomal protein L19 - Bacillus stearothermophilus 89 76 216 49 9 8363 10342 gi|153792 recP peptide [Streptococcus pneumoniae] 89 83 1980 51 14 18410 19447 gi|308857 ATP:D-fructose 6-phosphate 1-phosphotransferase 89 81 1038 [Lactococcus lactis] 57 11 9686 10669 gnl|PID|d100932 H2O-forming NADH Oxidase [Streptococcus mutans] 89 77 984 65 5 2418 2786 gi|1165307 S19 [Bacillus subtilis] 89 81 369 65 8 3806 4225 sp|P14577|RL16_(—) 50S RIBOSOMAL PROTEIN L16. 89 82 420 65 18 8219 8719 gi|143417 ribosomal protein S5 [Bacillus stearothermophilus] 89 76 501 73 9 6337 5315 gi|532204 prs [Listeria monocytogenes] 89 70 1023 76 3 3360 1465 gnl|PID|e200671 lepA gene product [Bacillus subtilis] 89 76 1896 99 10 12818 11919 gi|153738 membrane protein [Streptococcus mutans] 89 73 900 120 2 3552 1300 gi|407881 stringent response-like protein [Streptococcus equisimilis] 89 79 2253 122 5 4512 2791 gnl|PID|e280490 unknown [Streptococcus pneumoniae] 89 81 1722 176 1 669 4 gi|47394 5-oxoprolyl-peptidase [Streptococcus pyogenes] 89 78 666 177 6 3050 3934 gi|912423 putative [Lactococcus lactis] 89 71 885 181 8 4033 5751 gi|149411 enzyme III [Lactococcus lactis] 89 80 1719 211 4 3149 2793 gi|535273 aminopeptidase C [Streptococcus thermophilus] 89 83 357 361 1 431 838 gi|1196922 unknown protein [Insertion sequence IS861] 89 70 408 34 17 11839 10535 sp|P30053|SYH_S HISTIDYL-TRNA SYNTHETASE (EC 6.1.1.21) 88 78 1305 (HISTIDINE- TRNA LIGASE) (HISRS). 38 3 1646 2623 gi|2058544 putative ABC transporter subunit ComYA 88 78 978 [Streptococcus gordonii] 54 1 3 227 gnl|PID|d101320 YqgU [Bacillus subtilis] 88 66 225 57 2 611 1468 gnl|PID|e134943 putative reductase 1 [Saccharomyces cerevisiae] 88 75 858 65 13 5497 6069 pir|A29102|R5BS ribosomal protein L5 - Bacillus stearothermophilus 88 75 573 65 20 9030 9500 gi|2078381 ribosomal protein L15 [Staphylococcus aureus] 88 83 471 78 3 3636 1108 gnl|PID|d100781 lysyl-aminopeptidase [Lactococcus lactis] 88 80 2529 106 12 12965 12054 gi|2407215 (AF017421) putative heat shock protein HtpX 88 72 912 [Streptococcus gordonii] 107 2 219 962 gnl|PID|e339862 putative acylneuraminate lyase [Clostridium tertium] 88 75 744 111 8 14073 10420 gi|402363 RNA polymerase beta-subunit [Bacillus subtilis] 88 74 3654 126 9 13096 12062 gnl|PID|e311468 unknown [Bacillus subtilis] 88 74 1035 140 17 19143 18874 gi|1573659 H. influenzae predicted coding region HI0659 88 61 270 [Haemophilus influenzae] 144 1 394 555 gnl|PID|e274705 lactate oxidase [Streptococcus iniae] 88 75 162 148 4 2723 3493 gi|1591672 phosphate transport system ATP-binding protein 88 68 771 [Methanococcus jannaschii] 160 8 5853 6278 gi|1773267 ATPase, epsilon subunit [Streptococcus mutans] 88 65 426 177 4 1770 2885 gi|149426 putative [Lactococcus lactis] 88 72 1116 211 6 4140 3613 gi|535273 aminopeptidase C [Streptococcus thermophilus] 88 74 528 231 4 580 957 gi|40186 homologous to E. coli ribosomal protein L27 [Bacillus subtilis] 88 78 378 260 5 2387 2998 gi|1196922 unknown protein [Insertion sequence IS861] 88 69 612 291 6 2017 3375 gnl|PID|d100571 adenylosuccinate synthetase [Bacillus subtilis] 88 75 1359 319 4 658 317 gi|603578 serine/threonine kinase [Phytophthora capsici] 88 88 342 40 5 4353 4514 gi|153672 lactose repressor [Streptococcus mutans] 87 56 162 49 10 10660 10929 gi|1196921 unknown protein [Insertion sequence IS861] 87 72 270 65 7 3140 3808 gi|1165309 S3 [Bacillus subtilis] 87 73 669 65 15 6623 7039 gi|1044978 ribosomal protein S8 [Bacillus subtilis] 87 73 417 75 8 5411 6625 gi|1877422 galactokinase [Streptococcus mutans] 87 78 1215 80 2 703 2805 gnl|PID|d101166 elongation factor G [Bacillus subtilis] 87 76 2103 82 1 541 248 gi|1196921 unknown protein [Insertion sequence IS861] 87 69 294 140 23 25033 23897 gnl|PID|e254999 phenylalany-tRNA synthetase beta subunit [Bacillus subtilis] 87 74 1137 214 14 10441 8516 gi|2281305 glucose inhibited division protein homolog GidA 87 75 1926 [Lactococcus lactis cremoris] 220 2 2742 874 gnl|PID|e324358 product highly similar to elongation factor EF-G 87 73 1869 [Bacillus subtilis] 260 4 2096 2389 gi|1196921 unknown protein [Insertion sequence IS861] 87 72 294 323 1 27 650 gi|897795 30S ribosomal protein [Pediococcus acidilactici] 87 73 624 357 1 154 570 gi|1044978 ribosomal protein S8 [Bacillus subtilis] 87 73 417 49 11 10927 11445 gi|1196922 unknown protein [Insertion sequence IS861] 86 63 519 59 12 7461 9224 gi|951051 relaxase [Streptococcus pneumoniae] 86 68 1764 65 4 1553 2401 pir|A02759|R5BS ribosomal protein L2 - Bacillus stearothermophilus 86 77 849 65 23 10957 11610 gi|44074 adenylate kinase [Lactococcus lactis] 86 76 654 82 4 4374 4856 gi|153745 mannitol-specific enzyme III [Streptococcus mutans] 86 72 483 102 4 4270 4986 gnl|PID|e264705 OMP decarboxylase [Lactococcus lactis] 86 76 717 106 6 7824 6880 gnl|PID|e137598 aspartate transcarbamylase [Lactobacillus leichmannii] 86 68 945 107 1 1 273 gnl|PID|e339862 putative acylneuraminate lyase [Clostridium tertium] 86 71 273 111 7 10432 6710 gnl|PID|e228283 DNA-dependent RNA polymerase [Streptococcus pyogenes] 86 80 3723 131 9 5704 4892 gi|1661193 polipoprotein diacylglycerol transferase [Streptococcus mutans] 86 71 813 134 7 6430 7980 gi|2388637 glycerol kinase [Enterococcus faecalis] 86 73 1551 146 11 7473 6583 gi|1591731 melvalonate kinase [Methanococcus jannaschii] 86 72 891 153 2 595 2010 gi|2160707 dipeptidase [Lactococcus lactis] 86 78 1416 154 1 2 1435 gi|1857246 6-phosphogluconate dehydrogenase [Lactococcus lactis] 86 74 1434 161 5 5025 6284 gi|47529 Unknown [Streptococcus salivarius] 86 66 1260 184 1 2 1483 gi|642667 NADP-dependent glyceraldehyde-3-phosphate dehydrogenase 86 73 1482 [Streptococcus mutans] 210 8 3659 6571 gi|153661 translational initiation factor IF2 [Enterococcus faecium] 86 76 2913 250 1 2 187 gi|1573551 asparagine synthetase A (asnA) [Haemophilus influenzae] 86 68 186 36 4 2644 3909 gi|2149909 cell division protein [Enterococcus faecalis] 85 73 1266 38 4 2475 3587 gi|2058545 putative ABC transporter subunit ComYB 85 72 1113 [Streptococcus gordonii] 38 5 3577 3915 gi|2058546 ComYC [Streptococcus gordonii] 85 80 339 57 5 2797 3789 gnl|PID|d101316 YqfJ [Bacillus subtilis] 85 72 993 82 5 4915 6054 gi|153746 mannitol-phosphate dehydrogenase [Streptococcus mutans] 85 68 1140 83 15 14690 15793 gi|143371 phosphoribosyl aminoimidazole synthetase (PUR-M) 85 69 1104 [Bacillus subtilis] 87 2 1417 2388 gi|1184967 ScrR [Streptococcus mutans] 85 69 972 108 3 2666 3154 gi|153566 ORF (19K protein) [Enterococcus faecalis] 85 67 489 127 2 312 692 gi|1044989 ribosomal protein S13 [Bacillus subtilis] 85 72 381 128 3 1534 2409 gi|1685110 tetrahydrofolate dehydrogenase/cyclohydrolase 85 71 876 [Streptococcus thermophilus] 137 7 2962 4767 gnl|PID|d100347 Na+-ATPase alpha subunit [Enterococcus hirae] 85 74 1806 170 2 2622 709 gnl|PID|d102006 (AB001488) FUNCTION UNKNOWN, SIMILAR 85 70 1914 PRODUCT IN E. COLI, H. INFLUENZAE AND NEISSERIA MENINGITIDIS. [Bacillus subtilis] 187 5 3760 4386 gi|727436 putative 20-kDa protein [Lactococcus lactis] 85 65 627 233 2 728 1873 gi|1163116 ORF-5 [Streptococcus pneumoniae] 85 67 1146 234 3 962 1255 gi|2293155 (AF008220) YtiA [Bacillus subtilis] 85 61 294 240 1 309 1931 gi|143597 CTP synthetase [Bacillus subtilis] 85 70 1623 6 1 199 1521 gi|508979 GTP-binding protein [Bacillus subtilis] 84 72 1323 10 4 4375 3443 gnl|PID|e339862 putative acylneuraminate lyase [Clostridium tertium] 84 70 933 14 1 63 2093 gi|520753 DNA topoisomerase I [Bacillus subtilis] 84 69 2031 19 4 1793 2593 gi|2352484 (AF005098) RNAseH II [Lactococcus lactis] 84 68 801 20 17 17720 19687 gnl|PID|d100584 cell division protein [Bacillus subtilis] 84 71 1968 22 28 21723 20884 gi|299163 alanine dehydrogenase [Bacillus subtilis] 84 68 840 30 10 7730 6792 gnl|PID|d100296 fructokinase [Streptococcus mutans] 84 75 939 33 9 5650 5300 gi|147194 phnA protein [Escherichia coli] 84 71 351 36 22 21551 20772 gi|310631 ATP binding protein [Streptococcus gordonii] 84 72 780 48 4 2837 2505 gi|882609 6-phospho-beta-glucosidase [Escherichia coli] 84 69 333 58 1 41 1516 gi|450849 amylase [Streptococcus bovis] 84 73 1476 59 10 6715 7116 gi|951053 ORF10, putative [Streptococcus pneumoniae] 84 74 402 62 1 21 644 gi|806487 ORF211; putative [Lactococcus lactis] 84 66 624 65 17 7779 8207 gi|1044980 ribosomal protein L18 [Bacillus subtilis] 84 73 429 65 21 9507 10397 gi|44073 SecY protein [Lactococcus lactis] 84 68 891 106 4 5474 2262 gnl|PID|e199387 carbamoyl-phosphate synthase [Lactobacillus plantarum] 84 73 3213 159 1 147 4 gi|806487 ORF211; putative [Lactococcus lactis] 84 63 144 163 4 4690 5910 gi|2293164 (AF008220) SAM synthase [Bacillus subtilis] 84 69 1221 192 1 46 1308 gi|495046 tripeptidase [Lactococcus lactis] 84 73 1263 348 1 671 6 gi|1787753 (AE000245) f346; 79 pct identical to 336 amino acids of 84 71 666 ADH1_ZYMMO SW: P20368 but has 10 additional N-ter residues [Escherichia coli] 3 4 1572 3575 gi|143766 (thrSv) (EC 6.1.1.3) [Bacillus subtilis] 83 65 2004 9 6 3893 3417 gnl|PID|d100576 single strand DNA binding protein [Bacillus subtilis] 83 68 477 17 15 7426 8457 gi|520738 comA protein [Streptococcus pneumoniae] 83 66 1032 20 12 13860 14144 gnl|PID|d100583 unknown [Bacillus subtilis] 83 61 285 23 4 3358 2606 gi|1788294 (AE000290) o238; This 238 aa orf is 40 pct 83 74 753 identical (5 gaps) to 231 residues of an approx. 248 aa protein YEBC_ECOLI SW: P24237 [Escherichia coli] 28 6 3304 3005 gi|1573659 H. influenzae predicted coding region 83 57 300 HI0659 [Haemophilus influenzae] 35 7 5108 3867 gi|311707 hypothetical nucleotide binding protein [Acholeplasma laidlawii] 83 63 1242 55 19 17932 17528 gi|537085 ORF_f141 [Escherichia coli] 83 59 405 55 20 18539 17919 gi|496558 orfX [Bacillus subtilis] 83 69 621 65 6 2795 3142 gi|1165308 L22 [Bacillus subtilis] 83 64 348 68 6 6877 6683 gi|1213494 immunoglobulin A1 protease [Streptococcus pneumoniae] 83 54 195 87 15 15112 14771 gnl|PID|e323522 putative rpoZ protein [Bacillus subtilis] 83 54 342 96 12 8963 9631 gi|47394 5-oxoprolyl-peptidase [Streptococcus pyogenes] 83 73 669 98 1 3 263 gi|1183885 glutamine-binding subunit [Bacillus subtilis] 83 55 261 120 4 7170 5233 gi|310630 zinc metalloprotease [Streptococcus gordonii] 83 72 1938 127 7 2998 4347 gi|1500567 M. jannaschii predicted coding region 83 72 1350 MJ1665 [Methanococcus jannaschii] 137 1 3 440 gi|472918 v-type Na-ATPase [Enterococcus hirae] 83 60 438 160 6 3466 4356 gi|1773265 ATPase, gamma subunit [Streptococcus mutans] 83 67 891 214 4 2278 2964 gi|663279 transposase [Streptococcus pneumoniae] 83 72 687 226 3 2367 2020 gi|142154 thioredoxin [Synechococcus PCC6301] 83 58 348 303 1 3 1049 gi|40046 phosphoglucose isomerase A 83 67 1047 (AA 1-449) [Bacillus stearothermophilus] 303 2 1155 1931 gi|289282 glutamyl-tRNA synthetase [Bacillus subtilis] 83 67 777 6 17 15370 14318 gi|633147 ribose-phosphate pyrophosphokinase [Bacillus caldolyticus] 82 64 1053 7 1 299 96 gi|143648 ribosomal protein L28 [Bacillus subtilis] 82 69 204 9 3 1479 1090 gi|385178 unknown [Bacillus subtilis] 82 46 390 9 7 4213 3899 gnl|PID|d100576 ribosomal protein S6 [Bacillus subtilis] 82 60 315 12 6 4688 3942 gnl|PID|d100571 unknown [Bacillus subtilis] 82 68 747 22 17 13422 14837 gi|520754 putative [Bacillus subtilis] 82 69 1416 22 18 14897 15658 gnl|PID|d101929 uridine monophosphate kinase [Synechocystis sp.] 82 62 762 33 16 11471 10641 gnl|PID|d101190 ORF4 [Streptococcus mutans] 82 68 831 35 9 7400 6255 gi|1881543 UDP-N-acetylglucosamine-2-epimerase 82 68 1146 [Streptococcus pneumoniae] 40 10 8003 7533 gi|1173519 riboflavin synthase beta subunit 82 68 471 [Actinobacillus pleuropneumoniae] 48 32 23159 23437 gi|1930092 outer membrane protein [Campylobacter jejuni] 82 61 279 52 14 13833 14765 gi|142521 deoxyribodipyrimidine photolyase [Bacillus subtilis] 82 61 933 60 4 4737 1849 gnl|PID|d102221 (AF001610) uvrA [Deinococcus radiodurans] 82 66 2889 62 4 2131 1457 gi|2246749 (AF009622) thioredoxin reductase [Listeria monocytogenes] 82 63 675 71 11 16586 17518 gnl|PID|e322063 ss-1,4-galactosyltransferase [Streptococcus pneumoniae] 82 60 933 73 13 9222 7837 gnl|PID|d100586 unknown [Bacillus subtilis] 82 65 1386 74 1 1 3771 gnl|PID|d101199 alkaline amylopullulanase [Bacillus sp.] 82 68 3771 83 9 3696 3983 gnl|PID|e305362 unnamed protein product [Streptococcus thermophilus] 82 52 288 86 11 10776 9394 gi|683583 5-enolpyruvylshikimate-3-phosphate 82 67 1383 synthase [Lactococcus lactis] 89 12 8295 9752 gi|40025 homologous to E. coli 50K [Bacillus subtilis] 82 66 1458 115 9 10347 8812 gnl|PID|d102090 (AB003927) phospho-beta-galactosidase 1 82 74 1536 [Lactobacillus gasseri] 118 1 1 1332 gnl|PID|d100579 seryl-tRNA synthetase [Bacillus subtilis] 82 71 1332 151 3 4657 6246 pir|S06097|S060 type I site-specific deoxyribonuclease 82 66 1590 (EC 3.1.21.3) CfrA chain S - Citrobacter freundii 173 6 4183 3503 gi|2313836 (AE000584) conserved hypothetical 82 68 681 protein [Helicobacter pylori] 177 12 5481 7442 gnl|PID|d101999 (AB001341) NcrB [Escherichia coli] 82 58 1962 193 2 178 576 pir|S08564|R3BS ribosomal protein S9 - Bacillus stearothermophilus 82 70 399 245 2 258 845 gi|146402 EcoA type I restriction-modification enzyme S 82 68 588 subunit [Escherichia coli] 9 5 3400 3146 gnl|PID|d100576 ribosomal protein S18 [Bacillus subtilis] 81 66 255 16 7 7484 8413 gi|1100074 tryptophanyl-tRNA synthetase [Clostridium longisporum] 81 70 930 20 11 10308 13820 gnl|PID|d100583 transcription-repair coupling factor [Bacillus subtilis] 81 63 3513 38 2 1232 1606 gi|2058543 putative DNA binding protein [Streptococcus gordonii] 81 63 375 45 2 3061 1751 gi|460259 enolase [Bacillus subtilis] 81 67 1311 46 1 2 1267 gi|431231 uracil permease [Bacillus caldolyticus] 81 61 1266 48 3 2453 1440 gnl|PID|d100453 Mannosephosphate Isomerase [Streptococcus mutans] 81 70 1014 54 2 1106 336 gi|154752 transport protein [Agrobacterium tumefaciens] 81 64 771 65 22 10306 10821 gi|44073 SecY protein [Lactococcus lactis] 81 66 516 89 4 3874 2603 gi|556886 serine hydroxymethyltransferase [Bacillus subtilis] 81 69 1272 99 16 19126 18929 gi|2313526 (AE000557) H. pylori predicted coding 81 75 198 region HP0411 [Helicobacter pylori] 106 7 8373 7822 gnl|PID|e199384 pyrR [Lactobacillus plantarum] 81 61 552 108 6 5054 6877 gi|1469939 group B oligopeptidase PepB [Streptococcus agalactiae] 81 66 1824 113 15 15899 18283 pir|S09411|S094 spoIIIE protein - Bacillus subtilis 81 65 2385 128 5 3359 3634 gi|1685111 orf1091 [Streptococcus thermophilus] 81 69 276 151 1 830 3211 gi|304896 EcoE type I restriction-modification enzyme R 81 59 2382 subunit [Escherichia coli] 159 11 6722 7837 gi|2239288 GMP synthetase [Bacillus subtilis] 81 69 1116 170 1 739 458 gnl|PID|d102006 (AB001488) FUNCTION UNKNOWN. [Bacillus subtilis] 81 55 282 191 2 1759 893 gi|149522 tryptophan synthase alpha subunit [Lactococcus lactis] 81 65 867 214 3 2290 1994 gi|157587 reverse transcriptase endonuclease [Drosophila virilis] 81 43 297 217 4 4415 4008 gi|466473 cellobiose phosphotransferase enzyme II′ 81 59 408 [Bacillus stearothermophilus] 262 2 569 868 gi|153675 tagatose 6-P kinase [Streptococcus mutans] 81 68 300 299 1 663 4 gnl|PID|e301154 StySKI methylase [Salmonella enterica] 81 60 660 366 2 376 83 gi|149521 tryptophan synthase beta subunit [Lactococcus lactis] 81 65 294 12 10 8766 9242 gi|1216490 DNA/pantothenate metabolism flavoprotein 80 64 477 [Streptococcus mutans] 17 11 6050 5748 gnl|PID|e305362 unnamed protein product [Streptococcus thermophilus] 80 67 303 17 16 8455 9066 gi|703126 leucocin A translocator [Leuconostoc gelidum] 80 59 612 18 3 2440 1613 gi|1591672 phosphate transport system ATP-binding protein 80 58 828 [Methanococcus jannaschii] 27 3 4248 1579 gi|452309 valyl-tRNA synthetase [Bacillus subtilis] 80 69 2670 28 7 3671 3288 gi|1573660 H. influenzae predicted coding region HI0660 80 63 384 [Haemophilus influenzae] 32 2 902 1933 gnl|PID|e264499 dihydroorotate dehydrogenase B [Lactococcus lactis] 80 66 1032 39 1 1 1266 gnl|PID|e234078 hom [Lactococcus lactis] 80 63 1266 52 5 4363 3593 gi|1183884 ATP-binding subunit [Bacillus subtilis] 80 57 771 54 5 4550 4744 gi|2198820 (AF004225) Cux/CDP(1B1); Cux/CDP 80 60 195 homeoprotein [Mus musculus] 59 11 7109 7486 gi|951052 ORF9, putative [Streptococcus pneumoniae] 80 68 378 65 3 1230 1550 pir|A02815|R5BS ribosomal protein L23 - Bacillus stearothermophilus 80 69 321 65 12 5174 5503 pir|A02819|R5BS ribosomal protein L24 - Bacillus stearothermophilus 80 70 330 66 9 9884 10687 gi|2313836 (AE000584) conserved hypothetical protein 80 66 804 [Helicobacter pylori] 82 2 648 2438 gi|622991 mannitol transport protein [Bacillus stearothermophilus] 80 65 1791 85 1 950 630 gi|528995 polyketide synthase [Bacillus subtilis] 80 46 321 89 8 6870 5779 gi|853776 peptide chain release factor 1 [Bacillus subtilis] 80 63 1092 93 12 8718 7438 gnl|PID|d101959 hypothetical protein [Synechocystis sp.] 80 60 1281 106 5 6854 5751 gnl|PID|e199386 glutaminase of carbamoyl-phosphate synthase 80 65 1104 [Lactobacillus plantarum] 109 2 2160 1450 gi|40056 phoP gene product [Bacillus subtilis] 80 59 711 124 9 4246 3953 gnl|PID|d102254 30S ribosomal protein S16 [Bacillus subtilis] 80 65 294 128 8 5148 6428 gi|2281308 phosphopentomutase [Lactococcus lactis cremoris] 80 66 1281 137 19 12665 11376 gi|159109 NADP-dependent glutamate dehydrogenase 80 68 1290 [Giardia intestinalis] 140 19 19699 19457 gi|517210 putative transposase [Streptococcus pyogenes] 80 70 243 158 2 2474 984 gi|1877423 galactose-1-P-uridyl transferase [Streptococcus mutans] 80 65 1491 171 10 7474 7728 gi|397800 cyclophilin C-associated protein [Mus musculus] 80 60 255 181 1 2 619 gi|149395 lacC [Lactococcus lactis] 80 66 618 313 1 27 539 gi|143467 ribosomal protein S4 [Bacillus subtilis] 80 70 513 329 2 1652 858 gi|533080 RecF protein [Streptococcus pyogenes] 80 63 795 371 1 2 958 gi|442360 ClpC adenosine triphosphatase [Bacillus subtilis] 80 58 957 8 7 4312 5580 gi|149435 putative [Lactococcus lactis] 79 64 1269 23 1 1175 135 gi|1542975 AbcB [Thermoanaerobacterium thermosulfurigenes] 79 61 1041 33 14 9244 8201 gnl|PID|e253891 UDP-glucose 4-epimerase [Bacillus subtilis] 79 62 1044 36 3 1242 2633 gnl|PID|e324218 ftsA [Enterococcus hirae] 79 58 1392 38 13 7155 8378 gi|405134 acetate kinase [Bacillus subtilis] 79 58 1224 55 7 9011 8229 gi|1146234 dihydrodipicolinate reductase [Bacillus subtilis] 79 56 783 65 19 8661 8915 gi|2078380 ribosomal protein L30 [Staphylococcus aureus] 79 68 255 69 4 3678 2128 gnl|PID|e311452 unknown [Bacillus subtilis] 79 64 1551 69 9 7881 7279 gi|677850 hypothetical protein [Staphylococcus aureus] 79 59 603 72 10 8491 9783 gnl|PID|d101091 hypothetical protein [Synechocystis sp.] 79 62 1293 80 3 2906 7300 gi|143342 polymerase III [Bacillus subtilis] 79 65 4395 82 14 13326 15689 gnl|PID|e255093 hypothetical protein [Bacillus subtilis] 79 65 2364 86 13 12233 11118 gi|683582 prephenate dehydrogenase [Lactococcus lactis] 79 58 1116 92 3 940 1734 gi|537286 triosephosphate isomerase [Lactococcus lactis] 79 65 795 98 6 4023 4742 gnl|PID|d100262 LivG protein [Salmonella typhimurium] 79 63 720 99 12 16315 14150 gi|153736 a-galactosidase [Streptococcus mutans] 79 64 2166 107 7 5684 6406 gi|460080 D-alanine:D-alanine ligase-related protein 79 58 723 [Enterococcus faecalis] 113 9 6858 8303 gi|466882 pps1; B1496_C2_189 [Mycobacterium leprae] 79 64 1446 151 10 13424 12213 gi|450686 3-phosphoglycerate kinase [Thermotoga maritima] 79 60 1212 162 2 1158 3017 gi|506700 CapD [Staphylococcus aureus] 79 67 1860 177 5 2876 3052 gi|912423 putative [Lactococcus lactis] 79 61 177 177 8 4198 4563 gi|149429 putative [Lactococcus lactis] 79 61 366 187 3 2728 2907 gnl|PID|d102002 (AB001488) FUNCTION UNKNOWN. [Bacillus subtilis] 79 53 180 189 7 3589 4350 gnl|PID|e183449 putative ATP-binding protein of ABC-type [Bacillus subtilis] 79 61 762 191 5 4249 3449 gi|149519 indoleglycerol phosphate synthase [Lactococcus lactis] 79 66 801 211 3 1805 2737 gi|147404 mannose permease subunit II-M-Man [Escherichia coli] 79 57 933 212 3 3863 3621 gnl|PID|e209004 glutaredoxin-like protein [Lactococcus lactis] 79 58 243 215 1 987 715 gi|2293242 (AF008220) arginine succinate synthase [Bacillus subtilis] 79 64 273 323 2 530 781 gi|897795 30S ribosomal protein [Pediococcus acidilactici] 79 67 252 380 1 694 2 gi|1184680 polynucleotide phosphorylase [Bacillus subtilis] 79 64 693 384 2 655 239 gi|143328 phoP protein (put.); putative [Bacillus subtilis] 79 59 417 6 3 2820 4091 gi|853767 UDP-N-acetylglucosamine 1-carboxyvinyltransferase 78 62 1272 [Bacillus subtilis] 8 1 50 1786 gi|149432 putative [Lactococcus lactis] 78 63 1737 9 1 351 124 gi|897793 y98 gene product [Pediococcus acidilactici] 78 59 228 15 8 7364 8314 gnl|PID|d100585 cysteine synthetase A [Bacillus subtilis] 78 63 951 20 10 9738 10310 gnl|PID|d100583 stage V sporulation [Bacillus subtilis] 78 58 573 20 16 17165 17713 gi|49105 hypoxanthine phosphoribosyltransferase [Lactococcus lactis] 78 59 549 22 22 17388 18416 gnl|PID|d101315 YqfE [Bacillus subtilis] 78 60 1029 22 27 20971 20612 gi|299163 alanine dehydrogenase [Bacillus subtilis] 78 59 360 34 8 7407 7105 gi|41015 aspartate-tRNA ligase [Escherichia coli] 78 55 303 35 8 6257 5196 gi|1657644 Cap8E [Staphylococcus aureus] 78 60 1062 40 11 9287 8001 gi|1173518 GTP cyclohydrase II/3,4-dihydroxy-2-butanone- 78 58 1287 4-phosphate synthase [Actinobacillus pleuropneumoniae] 48 31 22422 23183 gi|2314330 (AE000623) glutamine ABC transporter, 78 58 762 ATP-binding protein (glnQ) [Helicobacter pylori] 52 2 2101 1430 gi|1183887 integral membrane protein [Bacillus subtilis] 78 54 672 55 14 13605 12712 gnl|PID|d102026 (AB002150) YbbP [Bacillus subtilis] 78 58 894 55 17 16637 15612 gnl|PID|e313027 hypothetical protein [Bacillus subtilis] 78 51 1026 71 14 19756 19598 gi|179764 calcium channel alpha-1D subunit [Homo sapiens] 78 57 159 74 11 15031 14018 gi|1573279 Holliday junction DNA helicase (ruvB) 78 57 1014 [Haemophilus influenzae] 75 9 6623 7972 gi|1877423 galactose-1-P-uridyl transferase [Streptococcus mutans] 78 62 1350 81 12 12125 13906 gi|1573607 L-fucose isomerase (fucI) [Haemophilus influenzae] 78 66 1782 82 3 2423 4417 gi|153744 ORF X; putative [Streptococcus mutans] 78 64 1995 83 18 16926 18500 gi|143373 phosphoribosyl aminoimidazole carboxy formyl 78 63 1575 formyltransferase/inosine monophosphate cyclohydrolase (PUR-H(J)) [Bacillus subtilis] 83 20 20212 20775 gi|143364 phosphoribosyl aminoimidazole carboxylase I (PUR-E) 78 64 564 [Bacillus subtilis] 92 2 165 878 gnl|PID|d101190 ORF2 [Streptococcus mutans] 78 62 714 98 8 5863 6909 gi|2331287 (AF013188) release factor 2 [Bacillus subtilis] 78 63 1047 113 3 1071 2741 gi|580914 dnaZX [Bacillus subtilis] 78 64 1671 127 4 1133 2071 gi|142463 RNA polymerase alpha-core-subunit [Bacillus subtilis] 78 59 939 132 1 2782 497 gi|1561763 pullulanase [Bacteroides thetaiotaomicron] 78 58 2286 135 4 2698 3537 gi|1788036 (AE000269) NH3-dependent NAD synthetase [Escherichia coli] 78 66 840 140 24 26853 25423 gi|1100077 phospho-beta-glucosidase [Clostridium longisporum] 78 64 1431 150 5 4690 4514 gi|149464 amino peptidase [Lactococcus lactis] 78 42 177 152 1 1 795 gi|639915 NADH dehydrogenase subunit [Thunbergia alata] 78 43 795 162 4 4997 4110 gnl|PID|e323528 putative YhaP protein [Bacillus subtilis] 78 64 888 181 10 8651 7947 gi|149402 lactose repressor (lacR; alt.) [Lactococcus lactis] 78 48 705 200 4 3627 4958 gnl|PID|d100172 invertase [Zymomonas mobilis] 78 61 1332 203 3 3230 3015 gi|1174237 CycK [Pseudomonas fluorescens] 78 57 216 210 9 6789 7172 gi|580902 ORF6 gene product [Bacillus subtilis] 78 42 384 214 6 3810 2797 gnl|PID|d102049 P. haemolytica o-sialoglycoprotein endopeptidase; P36175 (660) 78 60 1014 transmembrane [Bacillus subtilis] 214 13 6322 8163 gi|1377831 unknown [Bacillus subtilis] 78 62 1842 217 1 9 2717 gi|488430 alcohol dehydrogenase 2 [Entamoeba histolytica] 78 64 2709 222 3 2316 3098 gi|1573047 spore germination and vegetative growth protein 78 65 783 (gerC2) [Haemophilus influenzae] 268 1 742 8 gi|517210 putative transposase [Streptococcus pyogenes] 78 65 735 276 1 223 753 gnl|PID|d100306 ribosomal protein L1 [Bacillus subtilis] 78 65 531 312 3 1567 1079 gi|289261 comE ORF2 [Bacillus subtilis] 78 54 489 339 1 117 794 gi|1916729 CadD [Staphylococcus aureus] 78 53 678 342 2 762 265 gi|1842439 phosphatidylglycerophosphate synthase [Bacillus subtilis] 78 59 498 383 1 737 3 gi|1184680 polynucleotide phosphorylase [Bacillus subtilis] 78 64 735 7 15 11923 11018 gi|1399855 carboxyltransferase beta subunit [Synechococcus PCC7942] 77 63 906 8 2 1698 2255 gi|149433 putative [Lactococcus lactis] 77 59 558 17 14 6948 7550 gi|520738 comA protein [Streptococcus pneumoniae] 77 60 603 30 12 9761 8967 gi|1000451 TreP [Bacillus subtilis] 77 43 795 36 14 11421 12131 gi|1573766 phosphoglyceromutase (gpmA) [Haemophilus influenzae] 77 64 711 55 3 3836 4096 gi|1708640 YeaB [Bacillus subtilis] 77 55 261 61 8 8377 8054 gi|1890649 multidrug resistance protein LmrA [Lactococcus lactis] 77 51 324 65 2 607 1254 gi|40103 ribosomal protein L4 [Bacillus stearothermophilus] 77 63 648 68 8 7509 7240 gi|47551 MRP [Streptococcus suis] 77 68 270 69 1 1083 118 gnl|PID|e311493 unknown [Bacillus subtilis] 77 57 966 77 5 4583 4026 gnl|PID|e281578 hypothetical 12.2 kd protein [Bacillus subtilis] 77 60 558 83 14 13104 14552 gi|1590947 amidophosphoribosyltransferase [Methanococcus jannaschii] 77 56 1449 94 4 3006 5444 gnl|PID|e329895 (AJ000496) cyclic nucleotide-gated channel beta 77 66 2439 subunit [Rattus norvegicus] 96 11 8518 8880 gi|551879 ORF 1 [Lactococcus lactis] 77 62 363 99 11 14082 12799 gi|153737 sugar-binding protein [Streptococcus mutans] 77 61 1284 106 2 361 1176 gi|148921 LicD protein [Haemophilus influenzae] 77 51 816 108 4 3152 4030 gi|1574730 tellurite resistance protein (tehB) [Haemophilus influenzae] 77 58 879 118 4 3520 3131 gi|1573900 D-alanine permease (dagA) [Haemophilus influenzae] 77 57 390 124 4 1796 1071 gi|1573162 tRNA (guanine-N1)-methyltransferase (trmD) 77 58 726 [Haemophilus influenzae] 126 4 5909 4614 gnl|PID|d101163 Srb [Bacillus subtilis] 77 62 1296 128 2 630 1373 gnl|PID|d101328 YqiZ [Bacillus subtilis] 77 58 744 130 1 1 1287 gnl|PID|e325013 hypothetical protein [Bacillus subtilis] 77 61 1287 139 5 4388 3639 gi|2293302 (AF008220) YtqA [Bacillus subtilis] 77 59 750 140 11 10931 9582 gi|289284 cysteinyl-tRNA synthetase [Bacillus subtilis] 77 64 1350 140 18 19451 19263 gi|517210 putative transposase [Streptococcus pyogenes] 77 66 189 141 2 976 1683 gnl|PID|e157887 URF5 (aa 1-573) [Drosophila yakuba] 77 50 708 141 4 2735 5293 gi|556258 secA [Listeria monocytogenes] 77 59 2559 144 2 671 2173 gnl|PID|d100585 lysyl-tRNA thynthetase [Bacillus subtilis] 77 61 1503 163 5 6412 7398 gi|511015 dihydroorotate dehydrogenase A [Lactococcus lactis] 77 62 987 164 10 7841 7074 gnl|PID|d100964 homologue of iron dicitrate transport ATP-binding 77 52 768 protein FecE of E. coli [Bacillus subtilis] 191 8 7257 5791 gi|149516 anthranilate synthase alpha subunit [Lactococcus lactis] 77 57 1467 198 8 5377 5177 gi|1573856 hypothetical [Haemophilus influenzae] 77 66 201 213 1 202 462 gi|1743860 Brca2 [Mus musculus] 77 50 261 250 2 231 509 gnl|PID|e334776 YlbH protein [Bacillus subtilis] 77 60 279 289 3 1737 1276 gnl|PID|d100947 Ribosomal Protein L10 [Bacillus subtilis] 77 62 462 292 2 1399 668 gi|143004 transfer RNA-Gln synthetase [Bacillus stearothermophilus] 77 58 732 7 3 2734 1166 gnl|PID|d101824 peptide-chain-release factor 3 [Synechocystis sp.] 76 53 1569 7 23 18474 18235 gi|455157 acyl carrier protein [Cryptomonas phi] 76 57 240 9 8 5706 4342 gi|1146247 asparaginyl-tRNA synthetase [Bacillus subtilis] 76 61 1365 10 5 4531 4385 gnl|PID|e314495 hypothetical protein [Clostridium perfringens] 76 53 147 18 2 1615 842 gi|1591672 phosphate transport system ATP-binding protein 76 56 774 [Methanococcus jannaschii] 22 37 27796 28173 gal|PID|e13389 translation initiation factor IF3 (AA 1-172) 76 64 378 [Bacillus stearothermophilus] 35 6 3869 2682 gi|1773346 Cap5G [Staphylococcus aureus] 76 61 1188 48 28 21113 21787 gi|2314328 (AE000623) glutamine ABC transporter, permease protein 76 52 675 (glnP) [Helicobacter pylori] 52 12 12881 13786 gi|142521 deoxyribodipyrimidine photolyase [Bacillus subtilis] 76 58 906 55 10 11521 10571 gnl|PID|e283110 femD [Staphylococcus aureus] 76 61 951 57 8 7824 6559 gi|290561 o188 [Escherichia coli] 76 47 1266 62 5 2406 2095 gnl|PID|e313024 hypothetical protein [Bacillus subtilis] 76 59 312 65 9 4223 4441 gi|40148 L29 protein (AA 1-66) [Bacillus subtilis] 76 58 219 68 2 1328 2371 gnl|PID|e284233 anabolic ornithine carbamoyltransferase 76 61 1044 [Lactobacillus plantarum] 69 8 7297 6005 gnl|PID|d101420 Pyrimidine nucleoside phosphorylase 76 61 1293 [Bacillus stearothermophilus] 73 12 7839 7267 gnl|PID|e243629 unknown [Mycobacterium tuberculosis] 76 53 573 74 5 8433 7039 gnl|PID|d102048 C. thermocellum beta-glucosidase; P26208 76 60 1395 (985) [Bacillus subtilis] 80 5 7643 7936 gi|2314030 (AE000599) conserved hypothetical protein 76 61 294 [Helicobacter pylori] 82 15 16019 16996 gi|1573900 D-alanine permease (dagA) [Haemophilus influenzae] 76 56 978 83 19 18616 19884 gi|143374 phosphoribosyl glycinamide synthetase (PUR-D; gtg start 76 60 1269 codon) [Bacillus subtilis] 86 14 13409 12231 gi|143806 AroF [Bacillus subtilis] 76 58 1179 87 1 3 1442 gi|153804 sucrose-6-phosphate hydrolase [Streptococcus mutans] 76 59 1440 87 16 15754 15110 gnl|PID|e323500 putative Gmk protein [Bacillus subtilis] 76 56 645 93 4 1769 1539 gi|1574820 1,4-alpha-glucan branching enzyme (glgB) 76 46 231 [Haemophilus influenzae] 94 1 51 365 gi|144313 6.0 kd ORF [Plasmid ColE1] 76 73 315 116 2 2151 1678 gi|153841 pneumococcal surface protein A [Streptococcus pneumoniae] 76 59 474 123 6 3442 5895 gi|1314297 ClpC ATPase [Listeria monocytogenes] 76 59 2454 126 2 2156 2932 gnl|PID|d101328 YqiZ [Bacillus subtilis] 76 61 777 128 10 6973 7797 gi|944944 purine nucleoside phosphorylase [Bacillus subtilis] 76 60 825 131 11 6186 5812 gi|1674310 (AE000058) Mycoplasma pneumoniae, MG085 76 47 375 homolog, from M. genitalium [ Mycoplasma pneumoniae] 139 4 3641 3192 gi|2293302 (AP008220) YtqA [Bacillus subtilis] 76 53 450 140 14 14872 12536 gi|1184680 polynucleotide phosphorylase [Bacillus subtilis] 76 62 2337 143 2 2583 3905 gi|143795 transfer RNA-Tyr synthetase [Bacillus subtilis] 76 61 1323 170 6 5095 6114 gnl|PID|d100959 ycgQ [Bacillus subtilis] 76 44 1020 180 2 1927 557 gi|40019 ORF 821 (aa 1-821) [Bacillus subtilis] 76 53 1371 191 7 5815 5228 gi|551880 anthranilate synthase beta subunit [Lactococcus lactis] 76 61 588 195 3 3829 2444 gi|2149905 D-glutamic acid adding enzyme [Enterococcus faecalis] 76 60 1386 200 3 1914 3629 gi|431272 lysis protein [Bacillus subtilis] 76 58 1716 201 1 431 207 gi|2208998 dextran glucosidase DexS [Streptococcus suis] 76 57 225 214 2 1283 2380 gi|663278 transposase [Streptococcus pneumoniae] 76 55 1098 225 3 2338 3411 gi|1552775 ATP-binding protein [Escherichia coli] 76 56 1074 233 1 2 724 gi|1163115 neuraminidase B [Streptococcus pneumoniae] 76 60 723 347 1 523 38 gi|537033 ORF_f356 [Escherichia coli] 76 60 486 356 2 842 165 gi|2149905 D-glutamic acid adding enzyme [Enterococcus faecalis] 76 61 678 366 3 734 348 gi|149520 phosphoribosyl anthranilate isomerase [Lactococcus lactis] 76 69 387 5 8 12599 11484 gi|1574293 fimbrial transcription regulation repressor (pilB) 75 61 1116 [Haemophilus influenzae] 6 13 12553 11894 gnl|PID|d102050 ydiH [Bacillus subtilis] 75 51 660 9 10 7282 6062 gi|142538 aspartate aminotransferase [Bacillus sp.] 75 55 1221 10 12 8080 7940 gi|149493 SCRFI methylase [Lactococcus lactis] 75 56 141 18 5 4266 3301 gnl|PID|d101319 YqgH [Bacillus subtilis] 75 52 966 22 4 1838 2728 gi|1373157 orf-X; hypothetical protein; Method: 75 62 891 conceptual translation supplied by author [Bacillus subtilis] 30 11 9015 7828 gi|153801 enzyme scr-II [Streptococcus mutans] 75 64 1188 31 5 2362 2030 gi|2293211 (AF008220) putative thioredoxin [Bacillus subtilis] 75 53 333 32 9 7484 8359 gnl|PID|d100560 formamidopyrimidine-DNA glycosylase [Streptococcus mutans] 75 61 876 33 4 1735 1448 gi|413976 ipa-52r gene product [Bacillus subtilis] 75 53 288 33 10 6470 5769 gi|533105 unknown [Bacillus subtilis] 75 56 702 33 12 6878 7183 pir|A00205|FECL ferredoxin [4Fe—4S] - Clostridium thermaceticum 75 56 306 36 1 181 2 gi|2088739 (AF003141) strong similarity to the 75 43 180 FABP/P2/CRBP/CRABP family of transporters [Caenorhabditis elegans] 38 22 14510 15379 gi|1574058 hypothetical [Haemophilus influenzae] 75 56 870 48 33 23398 24066 gi|1930092 outer membrane protein [Campylobacter jejuni] 75 56 669 51 1 2 319 gi|43985 nifS-like gene [Lactobacillus delbrueckii] 75 55 318 51 10 8318 11683 gi|537192 CG Site No. 620; alternate gene names hs, hsp, 75 50 3366 hsr, rm; apparent frameshift in GenBank Accession Number X06545 [Escherichia coli] 54 18 19566 20759 gi|666069 orf2 gene product [Lactobacillus leichmannii] 75 58 1194 57 9 8448 7822 gi|290561 o188 [Escherichia coli] 75 50 627 65 14 6072 6356 gi|606241 30S ribosomal subunit protein S14 [Escherichia coli] 75 64 285 70 4 3071 2472 gi|1256617 adenine phosphoribosyltransferase [Bacillus subtilis] 75 57 600 71 24 30399 29404 gi|1574390 C4-dicarboxylate transport protein [Haemophilus influenzae] 75 57 996 73 2 910 455 gnl|PID|e249656 YneT [Bacillus subtilis] 75 57 456 79 1 1810 491 gi|1146219 28.2% of identity to the Escherichia coli GTP-binding 75 59 1320 protein Era; putative [Bacillus subtilis] 82 6 6360 6536 gi|1655715 BztD [Rhodobacter capsulatus] 75 55 177 83 6 1938 2975 gnl|PID|e323529 putative PlsX protein [Bacillus subtilis] 75 56 1038 93 11 7368 5317 gi|39989 methionyl-tRNA synthetase [Bacillus stearothermophilus] 75 58 2052 93 13 9409 8699 gi|1591493 glutamine transport ATP-binding protein 75 54 711 Q [Methanococcus jannaschii] 95 1 1795 47 gnl|PID|e323510 YloV protein [Bacillus subtilis] 75 57 1749 103 2 362 1186 gnl|PID|e266928 unknown [Mycobacterium tuberculosis] 75 64 825 104 1 691 915 gi|460026 repressor protein [Streptococcus pneumoniae] 75 54 225 113 5 2951 3883 gnl|PID|d101119 ABC transporter subunit [Synechocystis sp.] 75 55 933 121 1 320 1390 gi|2145131 repressor of class I heat shock gene expression 75 58 1071 HrcA [Streptococcus mutans] 127 6 2614 3000 gi|1500451 M. jannaschii predicted coding region MJ1558 75 44 387 [Methanococcus jannaschii] 137 18 10082 10687 gi|393116 P-glycoprotein 5 [Entamoeba histolytica] 75 52 606 149 11 8499 9338 gnl|PID|d100582 unknown [Bacillus subtilis] 75 55 840 151 6 9100 7673 gi|40467 HsdS polypeptide, part of CfrA family [Citrobacter freundii] 75 57 1428 158 1 986 3 gnl|PID|e253891 UDP-glucose 4-epimerase [Bacillus subtilis] 75 63 984 172 8 5653 6774 gi|142978 glycerol dehydrogenase [Bacillus stearothermophilus] 75 56 1122 172 9 7139 9730 gnl|PID|e268456 unknown [Mycobacterium tuberculosis] 75 58 2592 173 1 261 79 gnl|PID|e236469 C10C5.6 [Caenorhabditis elegans] 75 50 183 185 3 3066 2014 gi|1574806 spermidine/putrescine transport ATP-binding protein (potA) 75 56 1053 [Haemophilus influenzae] 191 6 5235 4213 gi|149518 phosphoribosyl anthranilate transferase [Lactococcus lactis] 75 61 1023 226 2 1774 1181 gi|2314588 (AE000642) conserved hypothetical protein 75 65 594 [Helicobacter pylori] 231 1 1 153 gi|40173 homolog of E. coli ribosomal protein L21 [Bacillus subtilis] 75 57 153 234 1 2 418 gi|2293259 (AF008220) YtqI [Bacillus subtilis] 75 59 417 279 1 552 151 gi|1119198 unknown protein [Bacillus subtilis] 75 50 402 291 7 3558 3827 gi|40011 ORF17 (AA 1-161) [Bacillus subtilis] 75 48 270 375 2 137 628 gi|410137 ORFX13 [Bacillus subtilis] 75 58 492 6 20 16721 17560 gi|2293323 (AF008220) YtdI [Bacillus subtilis] 74 53 840 7 6 4682 6052 gi|1354211 PET112-like protein [Bacillus subtilis] 74 60 1371 18 4 3341 2427 gnl|PID|d101319 YqgI [Bacillus subtilis] 74 54 915 21 6 5885 4800 gi|1072381 glutamyl-aminopeptidase [Lactococcus lactis] 74 59 1086 24 2 739 548 gi|2314762 (AE000655) ABC transporter, permease protein (yaeE) 74 46 192 [Helicobacter pylori] 25 1 2 367 gnl|PID|d100932 H2O-forming NADH Oxidase [Streptococcus mutans] 74 63 366 38 18 11432 12964 gi|537034 ORF_o488 [Escherichia coli] 74 57 1533 48 10 8924 6669 gi|1513069 P-type adenosine triphosphatase [Listeria monocytogenes] 74 53 2256 55 11 11964 11401 gnl|PID|e283110 femD [Staphylococcus aureus] 74 64 564 61 2 1782 427 gi|2293216 (AF008220) putative UDP-N-acetylmuramate-alanine ligase 74 55 1356 [Bacillus subtilis] 76 10 9414 8065 gnl|PID|d101325 YqiB [Bacillus subtilis] 74 54 1350 83 2 666 926 pir|C33496|C334 hisC homolog - Bacillus subtilis 74 55 261 86 9 8985 8080 gi|683585 prephenate dehydratase [Lactococcus lactis] 74 55 906 102 5 5005 5652 gi|143394 OMP-PRPP transferase [Bacillus subtilis] 74 57 648 103 5 4364 3267 gnl|PID|e323524 YloN protein [Bacillus subtilis] 74 62 1098 108 7 6864 7592 gnl|PID|e257631 methyltransferase [Lactococcus lactis] 74 56 729 131 2 478 146 gnl|PID|d101320 YqgZ [Bacillus subtilis] 74 45 333 133 2 1380 919 gnl|PID|e313025 hypothetical protein [Bacillus subtilis] 74 60 462 137 9 6167 6787 gnl|PID|d100479 Na+-ATPase subunit D [Enterococcus hirae] 74 53 621 149 4 3008 3883 gnl|PID|d100581 high level kasgamycin resistance [Bacillus subtilis] 74 55 876 157 2 243 824 gi|1573373 methylated-DNA—protein-cysteine methyltransferase (dat1) 74 48 582 [Haemophilus influenzae] 164 6 3515 4249 gi|410131 ORFX7 [Bacillus subtilis] 74 48 582 167 7 5446 5201 gi|413927 ipa-3r gene product [Bacillus subtilis] 74 55 246 171 1 1 1818 gnl|PID|d102251 beta-galactosidase [Bacillus circulans] 74 62 1818 172 4 1064 2392 gi|466474 cellobiose phosphotransferase enzyme II” [Bacillus 74 50 1329 stearothermophilus] 185 1 326 3 gi|1573646 Mg(2+) transport ATPase protein C (mgtC) (SP: P22037) 74 68 324 [Haemophilus influenzae] 188 2 1089 2018 gi|1573008 ATP dependent translocator homolog (msbA) 74 44 930 [Haemophilus influenzae] 189 11 6491 7174 gi|1661199 sakacin A production response regulator [Streptococcus mutans] 74 60 684 210 2 520 1287 gi|2293207 (AF008220) YtmQ [Bacillus subtilis] 74 60 768 261 1 836 192 gi|666983 putative ATP binding subunit [Bacillus subtilis] 74 55 645 263 3 1619 3655 gi|663232 Similarity with S. cerevisiae hypothetical 137.7 kD 74 42 2037 protein in subtelomeric Y′ repeat region [Saccharomyces cerevisiae] 265 2 844 1227 gi|49272 Asparaginase [Bacillus licheniformis] 74 64 384 368 1 1 942 gi|603998 unknown [Saccharomyces cerevisiae] 74 39 942 7 16 13357 11921 gnl|PID|d101324 YqhX [Bacillus subtilis] 73 57 1437 17 10 5706 5449 gnl|PID|e305362 unnamed protein product [Streptococcus thermophilus] 73 47 258 31 2 522 244 gnl|PID|d100576 single strand DNA binding protein [Bacillus subtilis] 73 55 279 32 6 5667 6194 gnl|PID|d101315 YqfG [Bacillus subtilis] 73 58 528 34 15 10281 9790 gnl|PID|d102151 (AB001684) ORP42c [Chlorella vulgaris] 73 46 492 40 12 9876 9226 gi|1173517 riboflavin synthase alpha subunit 73 55 651 [Actinobacillus pleuropneumoniae] 55 2 3592 839 gnl|PID|d101887 cation-transporting ATPase PacL [Synechocystis sp.] 73 60 2754 55 18 17494 16586 gnl|PID|e265580 unknown [Mycobacterium tuberculosis] 73 52 909 65 16 7213 7767 gi|143419 ribosomal protein L6 [Bacillus stearothermophilus] 73 60 555 66 3 3300 3659 gnl|PID|e269883 LacF [Lactobacillus casei] 73 52 360 70 10 5557 5733 gi|857631 envelope protein [Human immunodeficiency virus type 1] 73 60 177 71 4 6133 8262 gnl|PID|e322063 ss-1,4-galactosyltransferase [Streptococcus pneumoniae] 73 45 2130 72 1 3 851 gi|2293177 (AF008220) transporter [Bacillus subtilis] 73 50 849 76 7 7019 6195 gnl|PID|d101325 YqiF [Bacillus subtilis] 73 66 825 76 12 10009 9533 gi|1573086 uridine kinase (uridine monophosphokinase) (udk) 73 54 477 [Haemophilus influenzae] 80 7 8113 9372 gi|1377823 aminopeptidase [Bacillus subtilis] 73 60 1260 97 5 3389 1668 gnl|PID|d101954 dihydroxyacid dehydratase [Synechocystis sp.] 73 54 1722 98 9 6912 7619 gnl|PID|e314991 FtsE [Mycobacterium tuberculosis] 73 54 708 108 11 10928 10440 gi|388109 regulatory protein [Enterococcus faecalis] 73 54 489 128 6 3632 4222 gi|1685111 orf1091 [Streptococcus thermophilus] 73 63 591 138 2 1575 394 gi|147326 transport protein [Escherichia coli] 73 60 1182 140 13 12538 11903 pir|E53402|E534 serine O-acetyltransferase (EC 2.3.1.30) - Bacillus 73 55 636 stearothermophilus 162 5 5701 4991 gnl|PID|e323511 putative YhaQ protein [Bacillus subtilis] 73 50 711 164 4 2323 2790 gi|1592076 hypothetical protein (SP: P25768) [Methanococcus jannaschii] 73 52 468 164 8 4815 5546 gi|410137 ORFX13 [Bacillus subtilis] 73 56 732 170 5 4394 5302 gnl|PID|d100959 homologue of unidentified protein of E. coli [Bacillus subtilis] 73 46 909 178 7 3893 4855 gi|46242 nodulation protein B, 5′end [Rhizobium loti] 73 56 963 204 6 5096 4278 gnl|PID|e214719 PlcR protein [Bacillus thuringiensis] 73 41 819 213 2 832 2037 gi|1565296 ribosomal protein S1 homolog; sequence specific 73 55 1206 DNA-binding protein [Leuconostoc lactis] 231 2 84 287 gi|40173 homolog of E. coli ribosomal protein L21 [Bacillus subtilis] 73 61 204 237 1 2 505 gi|1773151 adenine phosphoribosyltransferase [Escherichia coli] 73 51 504 269 1 2 691 gnl|PID|d101328 Yqix [Bacillus subtilis] 73 36 690 289 2 1272 832 pir|A02771|R7MC ribosomal protein L7/L12 - Micrococcus luteus 73 66 441 343 1 14 484 gi|1788125 (AE000276) hypothetical 30.4 kD protein in manZ-cspC 73 47 471 intergenic region [Escherichia coli] 356 1 222 4 gi|2149905 D-glutamic acid adding enzyme [Enterococcus faecalis] 73 50 219 7 5 3165 4691 gnl|PID|d101833 amidase [Synechocystis sp.] 72 52 1527 7 9 7195 7647 gi|146976 nusB [Escherichia coli] 72 54 453 7 17 13743 13300 gnl|PID|e289141 similar to hydroxymyristoyl-(acyl carrier protein) dehydratase 72 59 444 [Bacillus subtilis] 22 19 15637 16224 gnl|PID|d101929 ribosome releasing factor [Synechocystis sp.] 72 51 588 33 17 12111 11425 gnl|PID|d101190 ORF3 [Streptococcus mutans] 72 55 687 34 7 7147 5627 gi|396501 aspartyl-tRNA synthetase [Thermus thermophilus] 72 52 1521 38 23 15372 16085 pir|H64108|H641 L-ribulose-phosphate 4-epimerase (araD) homolog - 72 54 714 Haemophilus influenzae (strain Rd KW20) 39 5 5094 6905 gnl|PID|e254877 unknown [Mycobacterium tuberculosis] 72 56 1812 40 6 4469 4636 gi|153672 lactose repressor [Streptococcus mutans] 72 58 168 48 2 1459 1253 gi|310380 inhibin beta-A-subunit [Ovis aries] 72 33 207 48 29 21729 22424 gi|2314329 (AE000623) glutamine ABC transporter, permease 72 49 696 protein (glnP) [Helicobacter pylori] 50 5 4529 3288 gi|1750108 YnbA [Bacillus subtilis] 72 54 1242 51 3 1044 2282 gi|2293230 (AF008220) YtbJ [Bacillus subtilis] 72 54 1239 52 13 13681 13938 gi|142521 deoxyribodipyrimidine photolyase [Bacillus subtilis] 72 45 258 55 1 841 35 gi|882518 ORF_o304; GTG start [Escherichia coli] 72 59 807 75 5 2832 3191 gnl|PID|e209886 mercuric resistance operon regulatory protein [Bacillus subtilis] 72 44 360 76 6 6229 5771 gi|142450 ahrC protein [Bacillus subtilis] 72 53 459 79 5 5065 4592 gi|2293279 (AF008220) YtcG [Bacillus subtilis] 72 46 474 87 14 14726 12309 gnl|PID|e323502 putative PriA protein [Bacillus subtilis] 72 52 2418 91 1 444 662 gi|500691 MYO1 gene product [Saccharomyces cerevisiae] 72 50 219 91 7 4516 4764 gi|829615 skeletal muscle sodium channel alpha-subunit [Equus caballus] 72 38 249 95 2 2004 1717 gnl|PID|e323527 putative Asp23 protein [Bacillus subtilis] 72 40 288 109 1 1452 118 gi|143331 alkaline phosphatase regulatory protein [Bacillus subtilis] 72 52 1335 126 1 3 2192 gnl|PID|d101831 glutamine-binding periplasmic protein [Synechocystis sp.] 72 46 2190 130 3 1735 2478 gi|2415396 (AF015775) carboxypeptidase [Bacillus subtilis] 72 53 744 137 6 2585 2929 gi|472922 v-type Na-ATPase [Enterococcus hirae] 72 46 345 140 10 9601 9203 gi|49224 URF 4 [Synechococcus sp.] 72 48 399 146 5 1906 1247 gnl|PID|e324945 hypothetical protein [Bacillus subtilis] 72 45 660 147 2 2084 1083 gnl|PID|e325016 hypothetical protein [Bacillus subtilis] 72 56 1002 147 5 6156 5146 gi|472327 TPP-dependent acetoin dehydrogenase beta-subunit 72 56 1011 [Clostridium magnum] 148 8 5381 6433 gi|974332 NAD(P)H-dependent dihydroxyacetone-phosphate reductase 72 54 1053 [Bacillus subtilis] 148 14 10256 9675 gnl|PID|d101319 YqgN [Bacillus subtilis] 72 50 582 159 8 4005 4949 gi|1788770 (AE000330) o463; 24 pct identical (44 gaps) to 72 43 945 338 residues from penicillin-binding protein 4*, PBPE_BACSU SW: P32959 (451 aa) [Escherichia coli] 172 10 9907 10620 gi|763387 unknown [Saccharomyces cerevisiae] 72 55 714 220 3 2862 3602 gi|1574175 hypothetical [Haemophilus influenzae] 72 50 741 267 1 3 449 gi|290513 f470 [Escherichia coli] 72 48 447 281 2 899 540 gnl|PID|d100964 homologue of aspartokinase 2 alpha and beta subunits LysC of 72 45 360 B. subtilis [Bacillus subtilis] 290 1 1018 14 gi|474195 This ORF is homologous to a 40.0 kd hypothetical protein 72 54 1005 in the htrB 3′region from E. coli, Accession Number X61000 [Mycoplasma-like organism] 300 1 63 587 gi|746399 transcription elongation factor [Escherichia coli] 72 50 525 316 1 1326 4 gi|158127 protein kinase C [Drosophila melanogaster] 72 40 1323 342 1 227 3 gnl|PID|d101164 unknown [Bacillus subtilis] 72 54 225 354 1 1 1005 gnl|PID|d102048 C. thermocellum beta-glucosidase; P26208 (985) 72 52 1005 [Bacillus subtilis] 6 10 8134 10467 gnl|PID|e264229 unknown [Mycobacterium tuberculosis] 71 57 2334 7 20 16231 15464 gi|18046 3-oxoacyl-[acyl-carrier protein]reductase [Cuphea lanceolata] 71 52 768 15 1 1297 2 gnl|PID|d100571 replicative DNA helicase [Bacillus subtilis] 71 51 1296 15 4 4435 3869 gi|499384 orf189 [Bacillus subtilis] 71 47 567 18 6 5120 4218 gnl|PID|d101318 YqgG [Bacillus subtilis] 71 51 903 29 1 1 540 gi|1773142 similar to the 20.2 kd protein in TETB-EXOA region of 71 56 540 B. subtilis [Escherichia coli] 38 20 13327 13830 gi|537036 ORF_o158 [Escherichia coli] 71 48 504 51 12 15015 12676 gi|149528 dipeptidyl peptidase IV [Lactococcus lactis] 71 55 2340 55 23 21040 20585 gi|2343285 (AF015453) surface located protein [Lactobacillus rhamnosus] 71 58 456 60 2 705 265 gnl|PID|d101320 Yqgz [Bacillus subtilis] 71 44 441 71 18 24679 26226 gi|580920 rodD (gtaA) polypeptide (AA 1-673) [Bacillus subtilis] 71 44 1548 71 25 30587 30360 gi|606028 ORF_o414; Geneplot suggests frameshift near 71 50 228 start but none found [Escherichia coli] 72 6 5239 6729 gi|580835 lysine decarboxylase [Bacillus subtilis] 71 48 1491 72 14 11991 12878 gi|624085 similar to rat beta-alanine synthetase encoded by GenBank 71 54 888 Accession Number S27881; contains ATP/GTP binding motif [Paramecium bursaria Chlorella virus 1] 73 11 7269 7033 gi|1906594 PN1 [Rattus norvegicus] 71 42 237 74 6 10385 8517 gi|1573733 prolyl-tRNA synthetase (proS) [Haemophilus influenzae] 71 52 1869 81 9 5772 6578 gi|147404 mannose permease subunit II-M-Man [Escherichia coli] 71 45 807 86 5 4602 3604 gnl|PID|e322063 ss-1,4-galactosyltransferase [Streptococcus pneumoniae] 71 53 999 105 4 3619 4707 gi|2323341 (AF014460) PepQ [Streptococcus mutans] 71 58 1089 106 13 13557 12955 gi|1519287 LemA [Listeria monocytogenes] 71 48 603 114 2 1029 1979 gi|310303 mosA [Rhizobium meliloti] 71 55 951 122 2 564 1205 gi|1649037 glutamine transport ATP-binding protein GLNQ 71 50 642 [Salmonella typhimurium] 132 5 9018 7063 gnl|PID|d102049 H. influenzae hypothetical ABC transporter; P44808 (974) 71 51 1956 [Bacillus subtilis] 140 1 1141 227 gi|1673788 (AE000015) Mycoplasma pneumoniae, fructose-bisphosphate 71 49 915 aldolase; similar to Swiss-Prot Accession Number P13243, from B. subtilis [Mycoplasma pneumoniae] 140 5 5635 4973 gnl|PID|d100964 homologue of hypothetical protein in a rapamycin synthesis 71 48 663 gene cluster of Streptomyces hygroscopicus [Bacillus subtilis] 141 7 7369 7845 gnl|PID|d102005 (AB001488) FUNCTION UNKNOWN, SIMILAR 71 51 477 PRODUCT IN E. COLI AND MYCOPLASMA PNEUMONIAE. [Bacillus subtilis] 193 1 1 165 gi|46912 ribosomal protein L13 [Staphylococcus carnosus] 71 59 165 194 3 2205 1594 gi|535351 CodY [Bacillus subtilis] 71 52 612 199 3 1510 1319 gi|2182574 (AE000090) Y4pE [Rhizobium sp. NGR234] 71 45 192 208 2 2616 3752 gi|1787378 (AE000213) hypothetical protein in purB 5′ region 71 57 1137 [Escherichia coli] 209 2 2022 1141 gi|41432 fepC gene product [Escherichia coli] 71 46 882 210 5 1911 3071 gi|49316 ORF2 gene product [Bacillus subtilis] 71 45 1161 210 6 3069 3386 gi|580900 ORF3 gene product [Bacillus subtilis] 71 48 318 212 2 3561 1381 gi|557567 ribonucleotide reductase R1 subunit 71 53 2181 [Mycobacterium tuberculosis] 233 3 2003 2920 gnl|PID|d101320 YqgR [Bacillus subtilis] 71 50 918 244 1 13 1053 gnl|PID|d100964 homologue of aspartokinase 2 alpha and beta subunits LysC 71 55 1041 of B. subtilis [Bacillus subtilis] 251 2 1008 1874 gi|755601 unknown [Bacillus subtilis] 71 46 867 282 2 906 712 gi|1353874 unknown [Rhodobacter capsulatus] 71 46 195 312 4 2137 1565 gnl|PID|d102245 (AB005554) yxbF [Bacillus subtilis] 71 34 573 338 1 3 683 gi|1591045 hypothetical protein (SP: P31466) [Methanococcus jannaschii] 71 48 681 346 1 3 164 gi|1591234 hypothetical protein (SP: P42297) [Methanococcus jannaschii] 71 36 162 374 1 619 2 gi|397526 clumping factor [Staphylococcus aureus] 71 23 618 377 1 688 2 gi|397526 clumping factor [Staphylococcus aureus] 71 23 687 3 8 7419 6958 gnl|PID|e269486 Unknown [Bacillus subtilis] 70 42 462 3 10 8395 9075 gnl|PID|e255543 putative iron dependant repressor [Staphylococcus epidermidis] 70 46 681 7 14 11024 10254 gnl|PID|d100290 undefined open reading frame [Bacillus stearothermophilus] 70 55 771 7 18 14213 13719 gnl|PID|d101090 biotin carboxyl carrier protein of acetyl-CoA carboxylase 70 56 495 [Synechocystis sp.] 9 2 1057 287 gnl|PID|d100581 unknown [Bacillus subtilis] 70 52 771 12 4 2610 1789 gnl|PID|d101195 yycJ [Bacillus subtilis] 70 52 822 21 2 2586 1846 gi|2293447 (AF008930) ATPase [Bacillus subtilis] 70 54 741 22 13 10955 11512 gi|1165295 Ydr540cp [Saccharomyces cerevisiae] 70 50 558 30 6 4315 3980 gi|39478 ATP binding protein of transport ATPases [Bacillus firmus] 70 51 336 31 1 370 113 gi|662792 single-stranded DNA binding protein [unidentified eubacterium] 70 36 258 33 15 10639 9521 gi|1161219 homolgous to D-amino acid dehydrogenase enzyme 70 50 1119 [Pseudomonas aeruginosa] 38 6 3812 4312 gi|2058547 ComYD [Streptococcus gordonii] 70 48 501 38 25 17986 18477 gi|537033 ORF_f356 [Escherichia coli] 70 58 492 40 13 11054 9846 gi|1173516 riboflavin-specific deaminase [Actinobacillus pleuropneumoniae] 70 52 1209 42 2 722 1954 gi|1146183 putative [Bacillus subtilis] 70 51 1233 43 3 2373 1612 gi|1591493 glutamine transport ATP-binding protein Q 70 48 762 [Methanococcus jannaschii] 45 8 9197 8049 gnl|PID|d102036 subunit of ADP-glucose pyrophosphorylase 70 54 1149 [Bacillus stearothermophilus] 59 2 567 956 gnl|PID|d100302 neopullulanase [Bacillus sp.] 70 42 390 60 3 1874 795 gnl|PID|e276466 aminopeptidase P [Lactococcus lactis] 70 48 1080 61 4 5553 2437 gnl|PID|e275074 SNF [Bacillus cereus] 70 51 3117 61 7 7914 6802 gi|1573037 cystathionine gamma-synthase (metB) [Haemophilus influenzae] 70 52 1113 63 7 5372 7222 gnl|PID|d100974 unknown [Bacillus subtilis] 70 54 1851 68 7 7126 6962 gi|1263014 emm18.1 gene product [Streptococcus pyogenes] 70 37 165 72 12 10081 10911 gi|2313093 (AE000524) carboxynorspermidine decarboxylase (nspC) 70 56 831 [Helicobacter pylori] 75 10 7888 8124 gi|1877423 galactose-1-P-uridyl transferase [Streptococcus mutans] 70 59 237 79 3 3424 2525 gi|39881 ORF 311 (AA 1-311) [Bacillus subtilis] 70 47 900 87 10 9369 7324 gnl|PID|e323506 putative Pkn2 protein [Bacillus subtilis] 70 52 2046 96 14 10640 11788 gi|1573209 tRNA-guanine transglycosylase (tgt) [Haemophilus influenzae] 70 52 1149 113 2 574 1086 gi|433630 A180 [Saccharomyces cerevisiae] 70 59 513 123 5 2901 3461 gnl|PID|d100585 unknown [Bacillus subtilis] 70 45 561 125 5 4593 4282 gnl|PID|e276474 capacitative calcium entry channel 1 [Bos taurus] 70 35 312 129 5 4500 3454 gnl|PID|d101314 YqeT [Bacillus subtilis] 70 47 1047 133 3 2608 1394 gi|2293312 (AF008220) YtfP [Bacillus subtilis] 70 50 1215 135 1 420 662 gnl|PID|e265530 yorfE [Streptococcus pneumoniae] 70 47 243 137 3 438 932 gi|472919 v-type Na-ATPase [Enterococcus hirae] 70 57 495 138 1 440 3 gi|147336 transmembrane protein [Escherichia coli] 70 42 438 140 16 18796 16364 gi|976441 N5-methyltetrahydrofolate homocysteine methyltransferase 70 53 2433 [Saccharomyces cerevisiae] 167 10 8263 6695 gi|149535 D-alanine activating enzyme [Lactobacillus casei] 70 52 1569 204 4 3226 2747 gnl|PID|d102049 E. coli hypothetical protein; P31805 (267) [Bacillus subtilis] 70 51 480 207 3 2627 2869 gnl|PID|e309213 racGAP [Dictyostelium discoideum] 70 45 243 282 3 1136 882 gi|1353874 unknown [Rhodobacter capsulatus] 70 50 255 6 21 17554 18453 gnl|PID|e233879 hypothetical protein [Bacillus subtilis] 69 44 900 6 22 18482 19471 gi|580883 ipa-88d gene product [Bacillus subtilis] 69 53 990 22 6 4682 5824 gi|2209379 (AF006720) ProJ [Bacillus subtilis] 69 48 1143 22 9 7992 8651 gnl|PID|d100580 unknown [Bacillus subtilis] 69 51 660 22 12 9871 10767 gnl|PID|d100581 unknown [Bacillus subtilis] 69 51 897 27 7 5857 5348 gnl|PID|d102012 (AB001488) FUNCTION UNKNOWN. [Bacillus subtilis] 69 28 510 36 10 7294 10116 gi|437916 isoleucyl-tRNA synthetase [Staphylococcus aureus] 69 53 2823 38 1 2 1090 gi|141900 alcohol dehydrogenase (EC 1.1.1.1) [Alcaligenes eutrophus] 69 48 1089 40 14 11333 11944 gi|1573280 Holliday junction DNA helicase (ruvA) 69 44 612 [Haemophilus influenzae] 40 15 11942 12517 gi|1573653 DNA-3-methyladenine glycosidase I (tagI) 69 50 576 [Haemophilus influenzae] 45 6 6947 5490 gi|580887 starch (bacterial glycogen) synthase [Bacillus subtilis] 69 47 1458 48 34 24932 24153 gnl|PID|e233870 hypothetical protein [Bacillus subtilis] 69 36 780 49 6 6183 6521 gi|396297 similar to phosphotransferase system enzyme II 69 50 339 [Escherichia coli] 49 8 7586 8338 gi|396420 similar to Alcaligenes eutrophus pHG1 D-ribulose-5-phosphate 69 49 753 3 epimerase [Escherichia coli] 55 6 8262 7033 gi|1146238 poly(A) polymerase [Bacillus subtilis] 69 50 1230 59 3 954 2333 gnl|PID|e313038 hypothetical protein [Bacillus subtilis] 69 54 1380 62 3 1170 1418 gnl|PID|d101915 hypothetical protein [Synechocystis sp.] 69 49 249 63 8 7298 7762 gi|293017 ORF3 (put.); putative [Lactococcus lactis] 69 42 465 66 4 3657 5081 gi|153755 phospho-beta-D-galactosidase (EC 3.2.1.85) 69 49 1425 [Lactococcus lactis cremoris] 66 5 5126 6829 gi|433809 enzyme II [Streptococcus mutans] 69 46 1704 71 6 10017 10664 gnl|PID|e322063 ss-1,4-galactosyltransferase [Streptococcus pneumoniae] 69 39 648 71 21 27730 27966 gnl|PID|d100649 DE-cadherin [Drosophila melanogaster] 69 30 237 77 1 1 237 gi|287870 groES gene product [Lactococcus lactis] 69 44 237 81 5 3622 4101 gi|1573605 fucose operon protein (fucU) [Haemophilus influenzae] 69 52 480 83 1 40 714 pir|C33496|C334 hisC homolog - Bacillus subtilis 69 46 675 83 16 15742 16335 gi|143372 phosphoribosyl glycinamide formyltransferase (PUR-N) 69 46 675 [Bacillus subtilis] 85 2 1212 916 gi|194097 IFN-response element binding factor 1 [Mus musculus] 69 48 297 91 5 3678 4274 gi|1574712 anaerobic ribonuleoside-triphosphate reductase activating 69 44 597 protein (nrdG) [Haemophilus influenzae] 98 5 3247 4032 gnl|PID|d100262 LivF protein [Salmonella typhimurium] 69 51 786 108 5 4085 5056 gnl|PID|e257629 transcription factor [Lactococcus lactis] 69 49 972 126 3 3078 4568 gnl|PID|d101329 YqjJ [Bacillus subtilis] 69 49 1491 131 6 4121 2889 gnl|PID|d101314 YqeR [Bacillus subtilis] 69 47 1233 136 2 1505 2299 gnl|PID|d100581 unknown [Bacillus subtilis] 69 47 795 149 5 3852 4763 gnl|PID|e323525 YloQ protein [Bacillus subtilis] 69 50 912 149 12 9336 10655 gi|151571 Homology with E. coli and P. aeruginosa lysA gene; 69 52 1320 product of unknown function; putative [Pseudomonas syringae] 153 4 3191 3829 gi|1710373 BrnQ [Bacillus subtilis] 69 44 639 169 3 849 2324 gnl|PID|d100582 temperature sensitive cell division [Bacillus subtilis] 69 49 1476 180 1 566 3 gi|488339 alpha-amylase [unidentified cloning vector] 69 50 564 212 1 1196 231 gi|1395209 ribonucleotide reductase R2-2 small subunit 69 53 966 [Mycobacterium tuberculosis] 226 1 2 661 pir|JQ2285|JQ22 nodulin-26 - soybean 69 41 660 233 5 3249 4766 gi|472918 v-type Na-ATPase [Enterococcus hirae] 69 56 1518 235 3 660 1766 gi|148945 methylase [Haemophilus influenzae] 69 43 1107 243 2 865 2361 gnl|PID|d100225 ORF5 [Barley yellow dwarf virus] 69 69 1497 251 3 2899 1967 gi|2289231 macrolide-efflux protein [Streptococcus agalactiae] 69 51 933 310 1 1 282 gnl|PID|e322442 peptide deformylase [Clostridium beijerinckii] 69 55 282 369 1 868 2 gi|397526 clumping factor [Staphylococcus aureus] 69 22 867 370 1 749 3 gi|397526 clumping factor [Staphylococcus aureus] 69 21 747 379 1 44 280 gnl|PID|d100649 DE-cadherin [Drosophila melanogaster] 69 30 237 388 1 260 72 gi|1787524 (AE000225) hypothetical 32.7 kD protein in trpL-btuR 69 44 189 intergenic region [Escherichia coli] 1 2 2006 3040 gnl|PID|d101809 ABC transporter [Synechocystis sp.] 68 43 1035 12 5 3958 2600 gi|2182992 histidine kinase [Lactococcus lactis cremoris] 68 45 1359 15 2 1790 1311 pir|S16974|R5BS ribosomal protein L9 - Bacillus stearothermophilus 68 56 480 16 6 7353 5701 gi|1787041 (AE000184) o530; This 530 aa orf is 33 pct identical (14 gaps) 68 45 1653 to 525 residues of an approx. 640 aa protein YHES_HAEIN SW: P44808 [Escherichia coli] 17 12 6479 6805 gi|553165 acetylcholinesterase [Homo sapiens] 68 68 327 20 13 14128 14505 gi|142700 P competence protein (ttg start codon) (put.); putative 68 40 378 [Bacillus subtilis] 22 32 24612 25397 gi|289262 comE ORF3 [Bacillus subtilis] 68 36 786 30 7 4548 4288 gi|311388 ORF1 [Azorhizobium caulinodans] 68 46 261 36 5 3911 4585 gi|1573041 hypothetical [Haemophilus influenzae] 68 54 675 46 6 5219 6040 gi|1790131 (AE000446) hypothetical 29.7 kD protein in ibpA-gyrB 68 47 822 intergenic region [Escherichia coli] 54 10 6235 7086 gi|882579 CG Site No. 29739 [Escherichia coli] 68 55 852 55 5 7069 5165 gnl|PID|d101914 ABC transporter [Synechocystis sp.] 68 45 1905 71 3 6134 5613 gi|1573353 outer membrane integrity protein (tolA) 68 50 522 [Haemophilus influenzae] 71 10 15342 16613 gi|580866 ipa-12d gene product [Bacillus subtilis] 68 31 1272 71 12 17560 18792 gi|44073 SecY protein [Lactococcus lactis] 68 35 1233 71 17 22295 24703 gi|1762349 involved in protein export [Bacillus subtilis] 68 50 2409 73 16 10208 9729 gi|1353537 dUTPase [Bacteriophage r1t] 68 51 480 86 18 17198 16011 gi|413943 ipa-19d gene product [Bacillus subtilis] 68 53 1188 87 17 17491 15866 gi|150209 ORF 1 [Mycoplasma mycoides] 68 43 1626 89 6 5139 4354 gi|1498824 M. jannaschii predicted coding region MJ0062 68 40 786 [Methanococcus jannaschii] 89 11 8021 8242 gi|150974 4-oxalocrotonate tautomerase [Pseudomonas putida] 68 43 222 97 8 6755 5394 gi|2367358 (AE000491) hypothetical 52.9 kD protein in aidB-rpsF 68 41 1362 intergenic region [Escherichia coli] 98 3 1418 2308 gnl|PID|d100261 LivA protein [Salmonella typhimurium] 68 40 891 99 13 16414 17280 gi|455363 regulatory protein [Streptococcus mutans] 68 50 867 115 3 5054 3693 gi|466474 cellobiose phosphotransferase enzyme II” 68 44 1362 [Bacillus stearothermophilus] 124 7 3394 3221 gnl|PID|d100702 cut14 protein [Schizosaccharomyces pombe] 68 56 174 125 2 2923 1922 gi|450566 transmembrane protein [Bacillus subtilis] 68 50 1002 132 2 4858 2888 gnl|PID|d101732 DNA ligase [Synechocystis sp.] 68 52 1971 140 7 7765 7580 gi|1209711 unknown [Saccharomyces cerevisiae] 68 47 186 150 1 539 3 gi|402490 ADP-ribosylarginine hydrolase [Mus musculus] 68 59 537 164 1 58 867 gnl|PID|e255114 glutamate racemase [Bacillus subtilis] 68 49 810 164 2 819 1835 gnl|PID|e255117 hypothetical protein [Bacillus subtilis] 68 50 1017 169 7 3946 4104 pir|B54545|B545 hypothetical protein - Lactococcus lactis subsp. 68 40 159 lactis plasmid pSL2 170 4 4247 4396 gi|304146 spore coat protein [Bacillus subtilis] 68 52 150 171 8 6002 7054 gi|38722 precursor (aa −20 to 381) [Acinetobacter calcoaceticus] 68 54 1053 198 3 2473 1871 gnl|PID|e313075 hypothetical protein [Bacillus subtilis] 68 46 603 211 2 969 1802 gi|1439528 EIIC-man [Lactobacillus curvatus] 68 45 834 214 8 4926 4231 gnl|PID|d102049 H. influenzae hypothetical protein; P43990 (182) 68 50 696 [Bacillus subtilis] 217 6 4955 5170 gnl|PID|e326966 similar to B. vulgaris CMS-associated 68 36 216 mitochondrial . . . (reverse transcriptase) [Arabidopsis thaliana] 218 7 3930 4745 gi|2293198 (AF008220) YtgP [Bacillus subtilis] 68 38 816 220 6 4628 4338 gnl|PID|e325791 (AJ000005) orf1 [Bacillus megaterium] 68 51 291 236 1 746 108 gi|410137 ORFX13 [Bacillus subtilis] 68 46 639 237 2 675 1451 gi|396348 homoserine transsuccinylase [Escherichia coli] 68 49 777 250 4 771 1229 gi|310859 ORF2 [Synechococcus sp.] 68 50 459 254 1 517 155 gi|1787105 (AE000189) o648 was o669; This 669 aa orf is 40 pct identical 68 44 363 (1 gaps) to 217 residues of an approx. 232 aa protein YBBA_HAEIN SW: P45247 [Escherichia coli] 337 1 1 774 gnl|PID|e261990 putative orf [Bacillus subtilis] 68 47 774 345 1 3 653 gi|149513 thymidylate synthase (EC 2.1.1.45) [Lactococcus lactis] 68 61 651 386 2 417 4 gi|1573353 outer membrane integrity protein (tolA) 68 51 414 [Haemophilus influenzae] 2 4 5722 4697 gi|1592141 M. jannaschii predicted coding region MJ1507 67 26 1026 [Methanococcus jannaschii] 3 6 5397 4591 gi|2293175 (AF008220) signal transduction regulator [Bacillus subtilis] 67 44 807 5 2 2301 574 gi|2313385 (AE000547) para-aminobenzoate synthetase (pabB) 67 48 1728 [Helicobacter pylori] 6 19 16063 16758 gi|413931 ipa-7d gene product [Bacillus subtilis] 67 41 696 22 8 7094 7897 gi|1928962 pyrroline-5-carboxylate reductase [Actinidia deliciosa] 67 51 804 29 10 8335 9072 gi|468745 gtcR gene product [Bacillus brevis] 67 41 738 31 3 1379 585 gi|2425123 (AF019986) PksB [Dictyostelium discoideum] 67 49 795 32 11 8849 10150 gi|42029 ORF1 gene product [Escherichia coli] 67 47 1302 36 16 14830 15546 gi|1592142 ABC transporter, probable ATP-binding subunit 67 43 717 [Methanococcus jannaschii] 38 9 4958 5392 gnl|PID|e214803 T22B3.3 [Caenorhabditis elegans] 67 47 435 38 21 13775 14512 gi|537037 ORF_o216 [Escherichia coli] 67 52 738 45 9 10428 9181 gi|551710 branching enzyme (glgB) (EC 2.4.1.18) 67 51 1248 [Bacillus stearothermophilus] 48 23 18344 17514 gi|413949 ipa-25d gene product [Bacillus subtilis] 67 50 831 50 2 1773 952 gnl|PID|d101330 YqjQ [Bacillus subtilis] 67 55 822 53 1 431 3 gi|1574291 fimbrial transcription regulation repressor (pilB) 67 40 429 [Haemophilus influenzae] 55 13 12740 11946 gnl|PID|e252990 ORF YDL037c [Saccharomyces cerevisiae] 67 51 795 61 9 9210 8329 gnl|PID|e264711 ATP-binding cassette transporter A [Staphylococcus aureus] 67 50 882 71 2 5614 6117 gi|1197667 vitellogenin [Anolis pulchellus] 67 36 504 81 7 4489 4983 gi|1142714 phosphoenolpyruvate:mannose phosphotransferase element IIB 67 42 495 [Lactobacillus curvatus] 83 7 2957 3214 gi|1276746 Acyl carrier protein [Porphyra purpurea] 67 37 258 86 8 8140 6809 gi|1147744 PSR [Enterococcus hirae] 67 45 1332 97 3 986 1366 gnl|PID|d102235 (AB000631) unnamed protein product [Streptococcus mutans] 67 43 381 102 1 601 1413 gi|682765 mccB gene product [Escherichia coli] 67 36 813 106 3 1109 1987 gi|148921 LicD protein [Haemophilus influenzae] 67 43 879 115 4 5982 5656 gi|895750 putative cellobiose phosphotransferase enzyme III 67 44 327 [Bacillus subtilis] 115 7 8421 8077 gi|466473 cellobiose phosphotransferase enzyme II’ 67 51 345 [Bacillus stearothermophilus] 127 13 8127 7021 gi|147326 transport protein [Escherichia coli] 67 45 1107 136 3 2215 2859 gnl|PID|d100581 unknown [Bacillus subtilis] 67 49 645 140 21 23317 20906 gnl|PID|d101912 phenylalanyl-tRNA synthetase [Synechocystis sp.] 67 43 2412 146 6 2894 1893 gi|2182994 histidine kinase [Lactococcus lactis cremoris] 67 44 1002 151 8 11476 11117 gnl|PID|d100085 ORF129 [Bacillus cereus] 67 48 360 160 10 7453 8646 gi|2281317 OrfB; similar to a Streptococcus pneumoniae putative 67 46 1194 membrane protein encoded by GenBank Accession Number X99400; inactivation of the OrfB gene leads to UV-sensitivity and to decrease of homologous recombination (plasmidic test) [Lactococcus l 163 3 3099 4505 gnl|PID|d101317 YqfR [Bacillus subtilis] 67 47 1407 167 8 6704 5454 gi|1161933 DltB [Lactobacillus casei] 67 45 1251 169 4 2322 2879 gnl|PID|d101331 YqkG [Bacillus subtilis] 67 41 558 171 11 7656 8384 gi|153841 pneumococcal surface protein A [Streptococcus pneumoniae] 67 50 729 188 3 1930 3723 gi|1542975 AbcB [Thermoanaerobacterium thermosulfurigenes] 67 46 1794 189 6 3599 3141 gnl|PID|e325178 Hypothetical protein [Bacillus subtilis] 67 52 459 205 3 1663 2211 gi|606073 ORF_o169 [Escherichia coli] 67 47 549 207 4 2896 3456 gi|2276374 DtxR/iron regulated lipoprotein precursor 67 49 561 [Corynebacterium diphtheriae] 217 3 4086 3703 gi|895750 putative cellobiose phosphotransferase enzyme III 67 42 384 [Bacillus subtilis] 246 2 291 662 gi|1842438 unknown [Bacillus subtilis] 67 43 372 252 1 2 745 gi|2351768 PspA [Streptococcus pneumoniae] 67 41 744 265 3 1134 1811 gi|2313847 (AB000585) L-asparaginase II (ansB) [Helicobacter pylori] 67 42 678 295 1 1 375 gi|2276374 DtxR/iron regulated lipoprotein precursor 67 43 375 [Corynebacterium diphtheriae] 1 7 4898 5146 gnl|PID|e255179 unknown [Mycobacterium tuberculosis] 66 56 249 3 1 389 3 gnl|PID|e269548 Unknown [Bacillus subtilis] 66 48 387 3 20 19267 20805 gi|39956 IIGlc [Bacillus subtilis] 66 50 1539 4 3 2545 2718 gi|1787564 (AE000228) phage shock protein C [Escherichia coli] 66 36 174 5 9 13197 12592 gi|1574291 fimbrial transcription regulation repressor (pilB) 66 46 606 [Haemophilus influenzae] 9 4 2872 1451 gnl|PID|e266928 unknown [Mycobacterium tuberculosis] 66 43 1422 12 2 1469 1200 gi|520407 orf2; GTG start codon [Bacillus thuringiensis] 66 42 270 15 12 10979 9897 gi|2314738 (AE000653) translation elongation factor EF-Ts (tsf) 66 49 1083 [Helicobacter pylori] 16 2 1312 734 gnl|PID|d102245 (AB005554) yxbF [Bacillus subtilis] 66 35 579 22 3 1372 1851 gi|1480916 signal peptidase type II [Lactococcus lactis] 66 38 480 22 7 5828 7096 gnl|PID|e206261 gamma-glutamyl phosphate reductase 66 51 1269 [Streptococcus thermophilus] 22 20 16194 17138 gnl|PID|e281914 YitL [Bacillus subtilis] 66 50 945 30 2 530 976 gi|2314379 (AE000627) ABC transporter, ATP-binding protein (yhcG) 66 40 447 [Helicobacter pylori] 32 1 199 984 gi|312444 ORF2 [Bacillus caldolyticus] 66 49 786 33 13 8352 7234 gi|1387979 44% identity over 302 residues with hypothetical 66 44 1119 protein from Synechocystis sp, accession D64006_CD; expression induced by environmental stress; some similarity to glycosyl transferases; two potential membrane-spanning helices [Bacillus subtil 34 6 5658 4708 gnl|PID|e250724 orf2 [Lactobacillus sake] 66 39 951 34 14 9792 9574 gi|1590997 M. jannaschii predicted coding region MJ0272 66 48 219 [Methanococcus jannaschii] 35 16 15163 14501 gi|1773352 Cap5M [Staphylococcus aureus] 66 46 663 36 9 6173 6976 gi|1518680 minicell-associated protein DivIVA [Bacillus subtilis] 66 35 804 36 11 10396 10824 bbs|155344 insulin activator factor, INSAF [human, Pancreatic 66 43 429 insulinoma, Peptide Partial, 744 aa] [Homo sapiens] 48 1 28 1419 gnl|PID|e325204 hypothetical protein [Bacillus subtilis] 66 50 1392 48 7 3810 4112 gi|2182574 (AE000090) Y4pE [Rhizobium sp. NGR234] 66 40 303 52 4 3595 2789 gi|388565 major cell-binding factor [Campylobacter jejuni] 66 52 807 54 3 2662 1076 gnl|PID|d101831 glutamine-binding periplasmic protein [Synechocystis sp.] 66 43 1587 61 10 9740 9183 gnl|PID|e154144 mdr gene product [Staphylococcus aureus] 66 44 558 72 13 10893 11993 gi|2313129 (AE000526) H. pylori predicted coding region HP0049 66 44 1101 [Helicobacter pylori] 74 9 13267 12476 gi|1573941 hypothetical [Haemophilus influenzae] 66 43 792 75 1 2 868 gi|1574631 nicotinamide mononucleotide transporter (pnuC) 66 48 867 [Haemophilus influenzae] 75 7 5303 4275 gi|41312 put. EBG repressor protein [Escherichia coli] 66 40 1029 82 7 6813 8123 gnl|PID|e255128 trigger factor [Bacillus subtilis] 66 53 1311 83 3 905 1219 pir|C33496|C334 hisC homolog - Bacillus subtilis 66 44 315 86 10 9407 8925 gi|683584 shikimate kinase [Lactococcus lactis] 66 41 483 88 10 7001 6060 gi|2098719 putative fimbrial-associated protein [Actinomyces naeslundii] 66 52 942 89 1 951 4 gi|410118 ORFX19 [Bacillus subtilis] 66 41 948 93 7 3661 2711 gi|1787936 (AE000260) f298; This 298 aa orf is 51 pct identical 66 49 951 (5 gaps) to 297 residues of an approx. 304 aa protein YCSN_BACSU SW: P42972 [Escherichia coli] 104 3 1805 3049 gi|1469784 putative cell division protein ftsW [Enterococcus hirae] 66 48 1245 106 14 13576 14253 gi|40027 homologous to E. coli gidB [Bacillus subtilis] 66 52 678 107 3 965 1864 gi|144858 ORF A [Clostridium perfringens] 66 49 900 112 7 5718 6593 gi|609332 DprA [Haemophilus influenzae] 66 43 876 115 1 3 302 gi|727367 Hyr1p [Saccharomyces cerevisiae] 66 56 300 122 1 3 566 gnl|PID|d101328 YqiY [Bacillus subtilis] 66 36 564 126 8 11759 11046 gnl|PID|d101163 ORF3 [Bacillus subtilis] 66 48 714 128 11 8201 8431 gi|726288 growth associated protein GAP-43 [Xenopus laevis] 66 41 231 131 8 4894 4508 gi|486661 TMnm related protein [Saccharomyces cerevisiae] 66 39 387 140 3 3236 2574 gi|40056 phoP gene product [Bacillus subtilis] 66 36 663 140 15 16318 15434 gi|1658189 5,10-methylenetetrahydrofolate reductase [Erwinia carotovora] 66 48 885 146 12 7926 7636 gnl|PID|d101140 transposase [Synechocystis sp.] 66 42 291 147 6 7137 6154 gi|472326 TPP-dependent acetoin dehydrogenase alpha-subunit 66 48 984 [Clostridium magnum] 149 6 4435 5430 gnl|PID|d101887 pentose-5-phosphate-3-epimerase [Synechocystis sp.] 66 46 996 149 13 10754 11575 gi|42371 pyruvate formate-lyase activating enzyme (AA 1-246) 66 42 822 [Escherichia coli] 186 4 2578 2270 gnl|PID|d101199 ORF11 [Enterococcus faecalis] 66 41 309 207 2 2340 2597 gnl|PID|e321893 envelope glycoprotein gp160 [Human 66 46 258 immunodeficiency virus type 1] 210 7 3358 3678 gi|49318 ORF4 gene product [Bacillus subtilis] 66 46 321 217 8 5143 5355 gi|49538 thrombin receptor [Cricetulus longicaudatus] 66 38 213 220 4 3875 3642 gi|466648 alternate name ORFD of L23635 [Escherichia coli] 66 33 234 223 1 1070 138 gnl|PID|e247187 zinc finger protein [Bacteriophage phigle] 66 45 933 224 2 1864 2640 gi|1176399 putative ABC transporter subunit [Staphylococcus epidermidis] 66 41 777 243 1 3 872 dbj||AB000617_2 (AB000617) YcdH [Bacillus subtilis] 66 45 870 268 2 891 568 gi|517210 putative transposase [Streptococcus pyogenes] 66 60 324 322 1 2 643 gi|1499836 Zn protease [Methanococcus jannaschii] 66 40 642 5 10 13909 13178 gi|1574292 hypothetical [Haemophilus influenzae] 65 34 732 6 11 10465 11190 gi|142854 homologous to E. coli radc gene product and to unidentified 65 48 726 protein from Staphylococcus aureus [Bacillus subtilis] 7 2 647 405 pir|C64146|C641 hypothetical protein HI0259 - 65 42 243 Haemophilus influenzae (strain Rd KW20) 7 7 6246 6821 gnl|PID|d101323 YqhU [Bacillus subtilis] 65 50 576 10 2 1873 1397 gi|1163111 ORF-1 [Streptococcus pneumoniae] 65 54 477 16 3 1428 2222 gnl|PID|e325010 hypothetical protein [Bacillus subtilis] 65 45 795 21 4 3815 3357 gnl|PID|e314910 hypothetical protein [Staphylococcus sciuri] 65 40 459 22 34 25776 26384 gi|1123030 CpxA [Actinobacillus pleuropneumoniae] 65 42 609 43 2 1648 290 gi|1044826 F14E5.1 [Caenorhabditis elegans] 65 38 1359 48 13 10062 10856 gi|1573390 hypothetical [Haemophilus influenzae] 65 45 795 48 22 17521 16883 gi|1573391 hypothetical [Haemophilus influenzae] 65 37 639 48 25 19027 18533 gnl|PID|e264484 YCR020c, len: 215 [Saccharomyces cerevisiae] 65 38 495 49 3 3856 5334 gi|1480429 putative transcriptional regulator [Bacillus stearothermophilus] 65 32 1479 50 6 5337 4519 gi|171963 tRNA isopentenyl transferase [Saccharomyces cerevisiae] 65 42 819 52 15 14728 15588 gi|1499745 M. jannaschii predicted coding region MJ0912 65 46 861 [Methanococcus jannaschii] 59 7 3963 4745 gi|496514 orf zeta [Streptococcus pyogenes] 65 42 783 68 3 2500 3483 gi|887824 ORF_o310 [Escherichia coli] 65 46 984 69 3 2171 1077 gnl|PID|e311453 unknown [Bacillus subtilis] 65 42 1095 69 7 6029 5325 gi|809660 deoxyribose-phosphate aldolase [Bacillus subtilis] 65 55 705 71 5 8536 9783 gi|1573224 glycosyl transferase lgtC (GP: U14554_4) 65 42 1248 [Haemophilus influenzae] 72 8 7664 8527 gnl|PID|e267589 Unknown, highly similar to several spermidine synthases 65 39 864 [Bacillus subtilis] 76 5 5773 4097 gnl|PID|d101723 DNA REPAIR PROTEIN RECN (RECOMBINATION 65 44 1677 PROTEIN N). [Escherichia coli] 76 9 8099 7875 gi|1574276 exodeoxyribonuclease, small subunit (xseB) 65 38 225 [Haemophilus influenzae] 84 2 2870 2352 gi|2313188 (AE000532) conserved hypothetical protein 65 41 519 [Helicobacter pylori] 86 15 14495 13407 gnl|PID|d101880 3-dehydroquinate synthase [Synechocystis sp.] 65 44 1089 87 3 3706 2423 gi|151259 HMG-CoA reductase (EC 1.1.1.88) [Pseudomonas mevalonii] 65 51 1284 88 3 2425 2736 gi|1098510 unknown [Lactococcus lactis] 65 30 312 89 2 1627 1007 gnl|PID|d102008 (AB001488) SIMILAR TO ORF14 OF 65 41 621 ENTEROCOCCUS FAECALIS TRANSPOSON TN916. [Bacillus subtilis] 111 6 6635 6186 gnl|PID|e246063 NM23/nucleoside diphosphate kinase [Xenopus laevis] 65 50 450 116 1 3 1016 gnl|PID|d101125 queuosine biosynthesis protein QueA [Synechocystis sp.] 65 44 1014 123 1 69 389 gi|498839 ORF2 [Clostridium perfringens] 65 36 321 123 7 6522 7190 gi|1575577 DNA-binding response regulator [Thermotoga maritima] 65 39 669 125 3 3821 2859 gnl|PID|e257609 sugar-binding transport protein [Anaerocellum thermophilum] 65 47 963 137 12 8015 7818 gi|2182574 (AE000090) Y4pE [Rhizobium sp. NGR234] 65 41 198 147 4 5021 3885 gi|472329 dihydrolipoamide acetyltransferase [Clostridium magnum] 65 47 1137 148 2 1053 1931 gnl|PID|d101319 YqgH [Bacillus subtilis] 65 42 879 151 2 3212 4687 gi|304897 EcoE type I restriction modification enzyme M subunit 65 50 1476 [Escherichia coli] 156 2 730 437 gi|310893 membrane protein [Theileria parva] 65 47 294 164 7 4256 4837 gi|410132 ORFX8 [Bacillus subtilis] 65 48 582 169 6 3192 3914 gi|1552737 similar to purine nucleoside phosphorylase (deoD) 65 41 723 [Escherichia coli] 176 4 2951 2220 gnl|PID|e339500 oligopeptide binding lipoprotein 65 43 732 [Streptococcus pneumoniae] 195 4 4556 3900 gi|1592142 ABC transporter, probable ATP-binding subunit 65 40 657 [Methanococcus jannaschii] 196 1 160 1572 gnl|PID|d102004 (AB001488) PROBABLE UDP-N- 65 51 1413 ACETYLMURAMOYLALANYL-D-GLUTAMYL-2, 6-DIAMINOLIGASE (EC 6.3.2.15). [Bacillus subtilis] 204 2 2246 1215 gi|143156 membrane bound protein [Bacillus subtilis] 65 37 1032 210 4 1544 1891 gi|49315 ORF1 gene product 65 48 348 [Bacillus subtilis] 242 2 1625 723 gi|1787540 (AE000226) f249; This 249 aa orf is 32 pct 65 42 903 identical (8 gaps) to 244 residues of an approx. 272 aa protein AGAR_ECOLI SW: P42902 [Escherichia coli] 284 1 1 900 gi|559861 clyM [Plasmid pAD1] 65 36 900 304 1 2 574 gnl|PID|e290934 unknown [Mycobacterium tuberculosis] 65 52 573 315 1 2 1483 gi|790694 mannuronan C-5-epimerase [Azotobacter vinelandii] 65 57 1482 320 1 3 569 gnl|PID|d102048 K. aerogenes, histidine utilization repressor; P12380 (199) 65 46 567 DNA binding [Bacillus subtilis] 358 1 1 309 gnl|PID|e323508 YloS protein [Bacillus subtilis] 65 55 309 2 7 7571 6696 gi|1498753 nicotinate-nucleotide pyrophosphorylase [Rhodospirillum 64 47 876 rubrum] 6 6 5924 6802 gnl|PID|d101111 methionine aminopeptidase [Synechocystis sp.] 64 52 879 8 4 3417 3686 gi|1045935 DNA helicase II [Mycoplasma genitalium] 64 58 270 11 4 3249 2689 gnl|PID|e265529 OrfB [Streptococcus pneumoniae] 64 46 561 15 7 6504 7145 gi|1762328 Ycr59c/YigZ homolog [Bacillus subtilis] 64 45 642 22 11 9548 9895 gnl|PID|d100581 unknown [Bacillus subtilis] 64 38 348 22 30 22503 23174 gi|289260 comE ORF1 [Bacillus subtilis] 64 44 672 26 7 14375 14199 gi|409286 bmrU [Bacillus subtilis] 64 30 177 27 2 1510 1334 gi|40795 DdeI methylase [Desulfovibrio vulgaris] 64 51 177 29 2 614 297 gi|2326168 type VII collagen [Mus musculus] 64 50 318 35 2 368 721 pir|JC1151|JC11 hypothetical 20.3K protein (insertion sequence IS1131) - 64 50 354 Agrobacterium tumefaciens (strain PO22) plasmid Ti 40 1 3 449 gi|46970 epiD gene product [Staphylococcus epidermidis] 64 41 447 40 7 4683 4976 gnl|PID|e325792 (AJ000005) glucose kinase [Bacillus megaterium] 64 45 294 45 7 8068 6920 gnl|PID|d102036 subunit of ADP-glucose pyrophosphorylase [Bacillus 64 40 1149 stearothermophilus] 51 2 301 1059 gi|43985 nifS-like gene [Lactobacillus delbrueckii] 64 54 759 51 13 15251 18397 gi|2293260 (AF008220) DNA-polymerase III alpha-chain [Bacillus subtilis] 64 46 3147 53 3 1157 555 gi|1574292 hypothetical [Haemophilus influenzae] 64 47 603 58 2 4236 1606 gi|1573826 alanyl-tRNA synthetase (alaS) [Haemophilus influenzae] 64 51 2631 66 1 3 1259 gi|895749 putative cellobiose phosphotransferase enzyme II” [Bacillus 64 42 1257 subtilis] 68 5 5213 6556 gi|436965 [malA] gene products [Bacillus stearothermophilus] 64 47 1344 69 6 5356 4949 gnl|PID|d101316 Cdd [Bacillus subtilis] 64 52 408 74 4 6948 5038 gi|726480 L-glutamine-D-fructose-6-phosphate amidotransferase [Bacillus 64 50 1911 subtilis] 75 3 1283 1465 bbs|133379 TLS-CHOP = fusion protein(CHOP = C/EBP transcription 64 57 183 factor, TLS = nuclear RNA-binding protein) [human, myxoid liposarcomas cells, Peptide Mutant, 462 aa9 [Homo sapiens] 81 13 14016 14231 gi|143175 methanol dehydrogenase alpha-10 subunit [Bacillus sp. 64 35 216 83 22 21851 22090 gnl|PID|d101315 YqfA [Bacillus subtilis] 64 44 240 87 11 10046 9300 gnl|PID|e323505 putative Ptc1 protein [Bacillus subtilis] 64 43 747 98 7 5032 5706 gnl|PID|e233880 hypothetical protein [Bacillus subtilis] 64 38 675 105 1 2 1276 gi|1657503 similar to S. aureus mercury(II) reductase [Escherichia coli] 64 45 1275 113 7 5136 6410 gnl|PID|d101119 NifS [Synechocystis sp.] 64 50 1275 119 1 2 1297 gnl|PID|e320520 hypothetical protein [Natronobacterium pharaonis] 64 37 1296 123 3 1125 2156 gnl|PID|e253284 ORF YDL244w [Saccharomyces cerevisiae] 64 40 1032 124 5 2331 1780 gnl|PID|d101884 hypothetical protein [Synechocystis sp.] 64 50 552 129 4 3467 2709 gnl|PID|d101314 YqeU [Bacillus subtilis] 64 52 759 131 1 152 3 gi|1377841 unknown [Bacillus subtilis] 64 42 150 137 11 7196 7549 ~pir|JC1151|JC11 hypothetical 20.3K protein (insertion sequence IS1131) - 64 50 354 Agrobacterium tumefaciens (strain PO22) plasmid Ti 139 3 3226 2651 gi|2293301 (AF008220) YtqB [Bacillus subtilis] 64 44 576 146 10 6730 5648 gi|1322245 mevalonate pyrophosphate decarboxylase [Rattus norvegicus] 64 45 1083 147 1 2 1018 gnl|PID|e137033 unknown gene product [Lactobacillus leichmannii] 64 46 1017 148 11 8430 8783 gi|2130630 (AF000430) dynamin-like protein [Homo sapiens] 64 28 354 156 7 4313 3612 gnl|PID|d102050 transmembrane [Bacillus subtilis] 64 31 702 157 4 1299 2114 gnl|PID|d100892 homologous to Gln transport system permease proteins 64 43 816 [Bacillus subtilis] 162 6 5880 6362 gi|517204 ORF1, putative 42 kDa protein [Streptococcus pyogenes] 64 58 483 164 13 9707 8769 gnl|PID|d100964 homologue of ferric anguibactin transport system permerase 64 40 939 protein FatD of V. anguillarum [Bacillus subtilis] 175 5 3906 4598 gi|534045 antiterminator [Bacillus subtilis] 64 39 693 189 10 6154 6507 gi|581307 response regulator [Lactobacillus plantarum] 64 33 354 191 4 3519 2863 gi|149520 phosphoribosyl anthranilate isomerase [Lactococcus lactis] 64 46 657 202 1 76 1140 gnl|PID|e293806 O-acetylhomoserine sulfhydrylase [Leptospira meyeri] 64 47 1065 224 1 234 1571 gi|1573393 collagenase (prtc) [Haemophilus influenzae] 64 42 1338 231 3 291 647 gi|40174 ORF X [Bacillus subtilis] 64 43 357 253 3 709 1089 pir|JC1151|JC11 hypothetical 20.3K protein (insertion sequence IS1131) - 64 50 381 Agrobacterium tumefaciens (strain PO22) plasmid Ti 265 1 820 2 gi|1377832 unknown [Bacillus subtilis] 64 31 819 297 1 1 660 gi|1590871 collagenase [Methanococcus jannaschii] 64 48 660 328 1 263 21 gi|992651 Gin4p [Saccharomyces cerevisiae] 64 41 243 5 4 8730 8098 gi|556885 Unknown [Bacillus subtilis] 63 48 633 10 6 5178 4483 gi|1573101 hypothetical [Haemophilus influenzae] 63 40 696 12 11 9324 9902 gi|806536 membrane protein [Bacillus acidopullulyticus] 63 42 579 15 10 8897 9187 gi|722339 unknown [Acetobacter xylinum] 63 40 291 17 2 1031 309 gnl|PID|e217602 PlnU [Lactobacillus plantarum] 63 32 723 18 8 7778 6975 gi|1377843 unknown [Bacillus subtilis] 63 45 804 26 4 9780 7078 gi|142440 ATP-dependent nuclease [Bacillus subtilis] 63 46 2703 29 5 3488 4192 gi|1377829 unknown [Bacillus subtilis] 63 35 705 34 11 8830 7988 gnl|PID|d101198 ORF8 [Enterococcus faecalis] 63 45 843 35 3 1187 876 gi|722339 unknown [Acetobacter xylinum] 63 39 312 48 15 12509 11691 gi|1573389 hypothetical [Haemophilus influenzae] 63 41 819 51 11 12719 12189 gi|142450 ahrC protein [Bacillus subtilis] 63 35 531 55 4 3979 5022 gi|1708640 YeaB [Bacillus subtilis] 63 41 1044 55 15 13669 14670 gnl|PID|e311502 thioredoxine reductase [Bacillus subtilis] 63 44 1002 68 10 9242 8919 sp|P37686|YIAY_(—) HYPOTHETICAL 40.2 KD PROTEIN IN AVTA-SELB 63 40 324 INTERGENIC REGION (F382). 86 7 6554 5685 gi|1574382 lic-1 operon protein (licD) [Haemophilus influenzae] 63 41 870 88 8 6085 5180 gi|2098719 putative fimbrial-associated protein [Actinomyces naeslundii] 63 43 906 96 8 5858 6484 gi|1052803 orflgyrb gene product [Streptococcus pneumoniae] 63 38 627 100 1 240 1940 gi|7171 fucosidase [Dictyostelium discoideum] 63 36 1701 104 4 3063 5765 gi|144985 phosphoenolpyruvate carboxylase [Corynebacterium 63 46 2703 glutamicum] 106 8 9189 8554 gi|533099 endonuclease III [Bacillus subtilis] 63 45 636 122 6 4704 4886 gnl|PID|d101139 transposase [Synechocystis sp.] 63 39 183 128 7 4517 5203 gnl|PID|d101434 orf2 [Methanobacterium thermoautotrophicum] 63 50 687 137 4 963 1547 gi|472920 v-type Na-ATPase [Enterococcus hirae] 63 27 585 142 7 4100 4585 gnl|PID|e313025 hypothetical protein [Bacillus subtilis] 63 44 486 159 5 1741 2571 gi|1787043 (AE000184) f271; This 271 aa orf is 24 pct identical (16 gaps) to 63 39 831 265 residues of an approx. 272 aa protein YIDA_ECOLI SW: P09997 [Escherichia coli] 171 12 8803 14406 gnl|PID|e324918 IgA1 protease [Streptococcus sanguis] 63 48 5604 177 1 3 347 gi|1773150 hypothetical 14.8 kd protein [Escherichia coli] 63 34 345 178 2 423 917 gi|722339 unknown [Acetobacter xylinum] 63 41 495 178 3 794 1012 gi|1591582 cobalamin biosynthesis protein N [Methanococcus jannaschii] 63 36 219 195 1 1377 175 gnl|PID|e324217 ftsQ [Enterococcus hirae] 63 33 1203 234 5 1739 1527 gi|1591582 cobalamin biosynthesis protein N [Methanococcus jannaschii] 63 36 213 249 1 81 257 gi|1000453 TreR [Bacillus subtilis] 63 41 177 283 1 127 1347 gi|396486 ORF8 [Bacillus subtilis] 63 44 1221 293 3 2804 3466 gi|722339 unknown [Acetobacter xylinum] 63 37 663 311 1 905 486 gi|1877424 UDP-galactose 4-epimerase [Streptococcus mutans] 63 46 420 324 1 2 556 gi|1477741 histidine periplasmic binding protein P29 [Campylobacter jejuni] 63 36 555 365 1 219 13 gi|2252843 (AF013293) No definition line found [Arabidopsis thaliana] 63 33 207 382 1 88 378 gi|722339 unknown [Acetobacter xylinum] 63 40 291 385 3 364 158 gi|2252843 (AF013293) No definition line found [Arabidopsis thaliana] 63 33 207 2 1 2495 288 gnl|PID|e325007 penicillin-binding protein [Bacillus subtilis] 62 42 2208 3 23 23374 24231 gnl|PID|e254993 hypothetical protein [Bacillus subtilis] 62 35 858 6 16 14320 13193 gnl|PID|e349614 nifS-like protein [Mycobacterium leprae] 62 37 1128 7 8 6819 7232 gnl|PID|d101324 YqhY [Bacillus subtilis] 62 32 414 7 19 15466 14207 gnl|PID|d101804 beta ketoacyl-acyl carrier protein synthase [Synechocystis sp.] 62 43 1260 7 21 17155 16229 gnl|PID|e323514 putative FabD protein [Bacillus subtilis] 62 46 927 7 24 19526 18519 gi|1276434 beta-ketoacyl-ACP synthase III [Cuphea wrightii] 62 37 1008 12 7 5904 4702 gi|1573768 A/G-specific adenine glycosylase (mutY) [Haemophilus 62 43 1203 influenzae] 12 9 8032 8793 gi|1591587 pantothenate metabolism flavoprotein [Methanococcus 62 33 762 jannaschii] 15 11 9678 9328 pir|JC1151|JC11 hypothetical 20.3K protein (insertion sequence IS1131) - 62 43 351 Agrobacterium tumefaciens (strain PO22) plasmid Ti 17 4 2609 2442 gi|1591081 M. jannaschii predicted coding region MJ0374 [Methanococcus 62 43 168 jannaschii] 17 5 3053 2835 gi|149570 role in the expression of lactacin F, part of the laf operon 62 44 219 [Lactobacillus sp.] 22 10 8627 9538 gnl|PID|d100580 similar to B. subtilis DnaH [Bacillus subtilis] 62 43 912 30 3 865 2043 gi|2314379 (AE000627) ABC transporter, ATP-binding protein (yhcG) 62 43 1179 [Helicobacter pylori] 33 5 2235 1636 gi|413976 ipa-52r gene product [Bacillus subtilis] 62 44 600 38 11 5689 6123 gi|148231 o251 [Escherichia coli] 62 34 435 40 17 14272 13328 gnl|PID|d101904 hypothetical protein [Synechocystis sp.] 62 43 945 42 1 3 311 gi|1146182 putative [Bacillus subtilis] 62 41 309 44 2 1267 4005 gi|1786952 (AE000176) o877; 100 pct identical to the first 86 residues of 62 43 2739 the 100 aa hypothetical protein fragment YBGB_ECOLT SW: P54746 [Escherichia coli] 48 12 9732 9304 gi|662920 repressor protein [Enterococcus hirae] 62 32 429 51 8 5664 7181 gnl|PID|e301153 StySKI methylase [Salmonella enterica] 62 44 1518 52 3 2791 2099 gi|1183886 integral membrane protein [Bacillus subtilis] 62 41 693 55 16 15702 14704 gnl|PID|e313028 hypothetical protein [Bacillus subtilis] 62 40 999 59 6 3418 3984 gi|2065483 unknown [Lactococcus lactis lactis] 62 32 567 63 5 4997 4809 gi|149771 pilin gene inverting protein (PivML) [Moraxella lacunata] 62 28 189 70 14 10002 10739 gi|992977 bplG gene product [Bordetella pertussis] 62 45 738 71 13 18790 20382 gi|1280135 coded for by C. elegans cDNA cm21e6; coded for by 62 62 1593 C. elegans cDNA cm01e2; similar to melibiose carrier protein (thiomethylgalactoside permease II) [Caenorhabditis elegans] 71 28 32217 32768 gnl|PID|d101312 YqeG [Bacillus subtilis] 62 35 552 74 7 11666 10383 gi|1552753 hypothetical [Escherichia coli] 62 38 1284 80 8 9370 9609 gnl|PID|d102002 (AB001488) FUNCTION UNKNOWN. [Bacillus subtilis] 62 46 240 97 10 9068 7041 gi|882463 protein-N(pi)-phosphohistidine-sugar phosphotransferase 62 42 2028 [Escherichia coli] 98 4 2306 3268 gnl|PID|d101496 BraE (integral membrane protein) [Pseudomonas aeruginosa] 62 42 963 102 3 2823 3539 gnl|PID|e313010 hypothetical protein [Bacillus subtilis] 62 24 717 103 3 2795 1242 gnl|PID|d102049 H. influenzae hypothetical ABC transporter; P44808 (974) 62 41 1554 [Bacillus subtilis] 111 2 2035 3462 gi|581297 NisP [Lactococcus lactis] 62 44 1428 112 4 3154 4080 gi|1574379 lic-1 operon protein (licA) [Haemophilus influenzae] 62 39 927 112 6 4939 5649 gi|1574381 lic-1 operon protein (licC) [Haemophilus influenzae] 62 39 711 124 3 1137 721 gi|1573024 anaerobic ribonucleoside-triphosphate reductase (nrdD) 62 45 417 [Haemophilus influenzae] 124 6 3162 2329 gi|609076 leucyl aminopeptidase [Lactobacillus delbrueckii] 62 40 834 126 7 11073 7516 gnl|PID|d101163 ORF4 [Bacillus subtilis] 62 38 3558 129 6 4983 4540 pir|S41509|S415 zinc finger protein EP6 - Chilo iridescent virus 62 48 444 131 7 4510 4103 gi|1857245 unknown [Lactococcus lactis] 62 42 408 149 2 1923 2579 gi|1592142 ABC transporter, probable ATP-binding subunit 62 41 657 [Methanococcus jannaschii] 149 7 5360 6055 gnl|PID|e323508 YloS protein [Bacillus subtilis] 62 40 696 156 1 450 238 gnl|PID|e254644 membrane protein [Streptococcus pneumoniae] 62 40 213 156 6 3606 2935 gnl|PID|d102050 transmembrane [Bacillus subtilis] 62 37 672 171 2 1779 2291 gi|43941 EIII-B Sor PTS [Klebsiella pneumoniae] 62 35 513 172 2 385 723 gi|895750 putative cellobiose phosphotransferase enzyme III 62 39 339 [Bacillus subtilis] 173 3 2599 893 gi|1591732 cobalt transport ATP-binding protein O 62 42 1707 [Methanococcus jannaschii] 179 2 492 1754 gi|1574071 H. influenzae predicted coding region HI1038 62 38 1263 [Haemophilus influenzae] 181 6 2856 3707 gi|1777435 LacT [Lactobacillus casei] 62 42 852 185 2 2074 311 gi|2182397 (AE000073) Y4fN [Rhizobium sp. NGR234] 62 41 1764 200 2 1061 1984 gi|450566 transmembrane protein [Bacillus subtilis] 62 37 924 202 3 2583 3473 gi|42219 P35 gene product (AA 1-314) [Escherichia coli] 62 41 891 210 3 1374 1565 gi|49315 ORF1 gene product [Bacillus subtilis] 62 45 192 211 1 3 971 gi|147402 mannose permease subunit III-Man [Escherichia coli] 62 43 969 223 2 1495 1034 gnl|PID|d101190 ORF2 [Streptococcus mutans] 62 41 462 228 1 34 909 gi|530063 glycerol uptake facilitator [Streptococcus pneumoniae] 62 44 876 234 2 90 917 gi|2293259 (AF008220) YtqI [Bacillus subtilis] 62 38 828 282 5 1765 1487 gnl|PID|e276475 galactokinase [Arabidopsis thaliana] 62 33 279 375 1 1 159 gi|1674231 (AE000052) Mycoplasma pneumoniae, hypothetical protein 62 40 159 homolog; similar to Swiss-Prot Accession Number P35155, from B. subtilis [Mycoplasma pneumoniae] 385 5 584 357 gi|1573353 outer membrane integrity protein (tolA) 62 47 228 [Haemophilus influenzae] 3 19 18550 19269 gi|606162 ORF_f229 [Escherichia coli] 61 41 720 7 4 2725 3225 gi|2114425 similar to Synechocystis sp. hypothetical protein, 61 42 501 encoded by GenBank Accession Number D64006 [Bacillus subtilis] 17 6 3326 3054 gi|149569 lactacin F [Lactobacillus sp.] 61 43 273 44 3 4061 4957 gnl|PID|d101068 xylose repressor [Synechocystis sp.] 61 38 897 54 11 8388 7234 gnl|PID|d101329 YqjH [Bacillus subtilis] 61 42 1155 57 6 3974 6037 gnl|PID|d101316 YqfK [Bacillus subtilis] 61 42 2064 58 5 7356 6565 sp|P45169|POTC_(—) SPERMIDINE/PUTRESCINE TPANSPORT 61 34 792 SYSTEM PERMEASE PROTEIN POTC. 67 1 3 692 gi|537108 ORF_f254 [Escherichia coli] 61 46 690 68 9 8816 7890 gi|19501 pPLZ12 gene product (AA 1-184) [Lupinus polyphyllus] 61 41 927 70 15 10737 12008 gi|992976 bplF gene product [Bordetella pertussis] 61 44 1272 72 11 9759 10202 gnl|PID|d101833 carboxynorspermidine decarboxylase [Synechocystis sp.] 61 36 444 76 8 7881 7003 gnl|PID|d100305 farnesyl diphosphate synthase [Bacillus stearothermophilus] 61 45 879 87 4 4914 3697 gi|528991 unknown [Bacillus subtilis] 61 42 1218 87 13 12311 11361 gi|1789683 (AE000407) methionyl-tRNA 61 44 951 formyltransferase [Escherichia coli] 91 2 731 2989 gi|537080 ribonucleoside triphosphate reductase [Escherichia coli] 61 45 2259 105 3 2711 3499 gnl|PID|d101851 hypothetical protein [Synechocystis sp.] 61 44 789 115 6 7968 6478 gi|895747 putative cel operon regulator [Bacillus subtilis] 61 36 1491 123 8 7181 8518 gi|1209527 protein histidine kinase [Enterococcus faecalis] 61 40 1338 126 6 7525 6725 gi|1787043 (AE000184) f271; This 271 aa orf is 24 61 38 801 pct identical (16 gaps) to 265 residues of an approx. 272 aa protein YIDA_ECOLI SW: P09997 [Escherichia coli] 128 1 1 639 gnl|PID|d101328 YqiY [Bacillus subtilis] 61 41 639 139 7 4794 5054 gi|1022726 unknown [Staphylococcus haemolyticus] 61 41 261 139 9 12632 5913 gnl|PID|e270014 beta-galactosidase [Thermoanaerobacter ethanolicus] 61 41 6720 143 1 2552 42 gi|520541 penicillin-binding proteins 1A and 1B [Bacillus subtilis] 61 42 2511 148 16 12125 11424 gi|1552743 tetrahydrodipicolinate N-succinyltransferase [Escherichia coli] 61 42 702 162 3 4112 3456 gnl|PID|d101829 phosphoglycolate phosphatase [Synechocystis sp.] 61 30 657 172 3 727 1077 gnl|PID|d102048 B. subtilis, cellobiose phosphotransferase 61 44 351 system, celA; P46318 (220) [Bacillus subtilis] 177 3 1101 1772 gnl|PID|d100574 unknown [Bacillus subtilis] 61 43 672 202 2 1278 2585 gi|1045831 hypothetical protein (GB: L18965_6) [Mycoplasma genitalium] 61 36 1308 224 3 2782 3144 gi|1591144 M. jannaschii predicted coding region MJ0440 61 30 363 [Methanococcus jannaschii] 225 4 3395 3766 gi|1552774 hypothetical [Escherichia coli] 61 40 372 249 2 212 802 gi|1000453 TreR [Bacillus subtilis] 61 42 591 254 2 843 484 gnl|PID|d100417 ORF120 [Escherichia coli] 61 36 360 257 1 3 350 gnl|PID|e255315 unknown [Mycobacterium tuberculosis] 61 42 348 293 4 3971 3657 pir|JC1151|JC11 hypothetical 20.3K protein (insertion 61 45 315 sequence IS1131) - Agrobacterium tumefaciens (strain PO22) plasmid Ti 301 1 949 17 gi|2291209 (AF016424) contains similarity to acyltransferases 61 33 933 [Caenorhabditis elegans] 373 1 1066 287 gi|393396 Tb-292 membrane associated protein 61 38 780 [Trypanosoma brucei subgroup] 3 24 24473 24955 gi|537093 ORF_o153b [Escherichia coli] 60 27 483 6 5 4636 5739 gi|2293258 (AF008220) YtoI [Bacillus subtilis] 60 35 1104 6 12 11936 11187 gi|293017 ORF3 (put.); putative [Lactococcus lactis] 60 44 750 17 13 6708 6484 gi|149569 lactacin F [Lactobacillus sp.] 60 32 225 18 7 6977 5670 gi|1788140 (AE000278) o481; This 481 aa orf is 60 43 1308 35 pct identical (19 gaps) to 309 residues of an approx. 856 aa protein NOL1_HUMAN SW: P46087 [Escherichia coli] 20 15 15878 17167 gnl|PID|d100584 unknown [Bacillus subtilis] 60 44 1290 22 1 1 243 gnl|PID|d102050 transmembrane [Bacillus subtilis] 60 36 243 32 10 8296 8964 gi|2293275 (AF008220) YtaG [Bacillus subtilis] 60 37 669 38 15 8837 9697 gi|40023 B. subtilis genes rpmH, rnpA, 50 kd, gidA and 60 35 861 gidB [Bacillus subtilis] 43 6 8610 5944 gi|171787 protein kinase 1 [Saccharomyces cerevisiae] 60 36 2667 44 1 1 1269 gnl|PID|e235823 unknown [Schizosaccharomyces pombe] 60 44 1269 45 10 11138 10368 gi|397488 1,4-alpha-glucan branching enzyme [Bacillus subtilis] 60 43 771 48 19 15766 14378 gnl|PID|e205173 orf1 [Lactobacillus helveticus] 60 39 1389 48 21 16727 16951 gnl|PID|d102041 (AB002668) unnamed protein product 60 32 225 [Haemophilus actinomycetemcomitans] 50 1 2 898 gnl|PID|e246537 ORF286 protein [Pseudomonas stutzeri] 60 31 897 62 2 638 1177 gnl|PID|d100587 unknown [Bacillus subtilis] 60 42 540 68 4 3590 5203 gi|1573583 H. influenzae predicted coding region HI0594 60 36 1614 [Haemophilus influenzae] 70 11 5781 6182 gnl|PID|d102014 (AB001488) SIMILAR TO YDFR GENE 60 33 402 PRODUCT OF THIS ENTRY (YDFR_BACSU). [Bacillus subtilis] 70 12 6343 8133 gnl|PID|e324970 hypothetical protein [Bacillus subtilis] 60 38 1791 71 8 11701 14157 gi|580866 ipa-12d gene product [Bacillus subtilis] 60 33 2457 74 8 12509 11664 gnl|PID|d101832 phosphatidate cytidylyltransferase [Synechocystis sp.] 60 45 846 76 4 4116 3367 gi|2352096 orf; similar to serine/threonine protein 60 39 750 phosphatase [Fervidobacterium islandicum] 80 4 7372 7665 gi|1786420 (AE000131) f86; 100 pct identical to GB: 60 30 294 ECODINJ_6 ACCESSION: D38582 [Escherichia coli] 81 6 4073 4522 gi|147402 mannose permease subunit III-Man [Escherichia coli] 60 35 450 86 1 940 155 gi|143177 putative [Bacillus subtilis] 60 26 786 92 1 1 192 gi|396348 homoserine transsuccinylase [Escherichia coli] 60 45 192 93 14 10619 9384 gi|1788389 (AE000297) o464; This 464 aa orf is 60 27 1236 33 pct identical (9 gaps) to 331 residues of an approx. 416 aa protein MTRC_NEIGO SW: P43505 [Escherichia coli] 94 5 5548 8121 gnl|PID|e329895 (AJ000496) cyclic nucleotide-gated channel beta 60 50 2574 subunit [Rattus norvegicus] 97 7 5396 4533 gi|1591396 transketolase' [Methanococcus jannaschii] 60 43 864 102 2 2081 2833 gnl|PID|e320929 hypothetical protein [Mycobacterium tuberculosis] 60 43 753 106 9 9773 9183 gnl|PID|e334782 YlbN protein [Bacillus subtilis] 60 31 591 113 8 6361 6837 gi|466875 nifU; B1496_C1_157 [Mycobacterium leprae] 60 43 477 115 2 2755 524 gnl|PID|e328143 (AJ000332) Glucosidase II [Homo sapiens] 60 32 2232 122 7 4763 5068 gnl|PID|d101876 transposase [Synechocystis sp.] 60 39 306 127 8 4510 5283 gi|1777938 Pgm [Treponema pallidum] 60 38 774 138 4 3082 2672 gnl|PID|e325196 hypothetical protein [Bacillus subtilis] 60 36 411 139 1 177 4 gnl|PID|d100680 ORF [Thermus thermophilus] 60 39 174 139 11 14520 13009 gi|537145 ORF_f437 [Escherichia coli] 60 30 1512 140 2 2592 1249 gi|1209527 protein histidine kinase [Enterococcus faecalis] 60 37 1344 141 1 210 1049 gi|463181 E5 ORF from bp 3842 to 4081; putative 60 34 840 [Human papillomavirus type 33] 141 5 5368 6405 gi|145362 tyrosine-sensitive DAHP synthase (aroF) [Escherichia coli] 60 41 1038 142 6 3558 4049 gi|600711 putative [Bacillus subtilis] 60 37 492 148 10 7742 8713 gnl|PID|e313022 hypothetical protein [Bacillus subtilis] 60 27 972 153 5 3667 4278 gi|2293322 (AF008220) branch-chain amino acid transporter 60 42 612 [Bacillus subtilis] 155 1 1413 748 gi|2104504 putative UDP-glucose dehydrogenase [Escherichia coli] 60 40 666 158 3 3116 2472 gnl|PID|d100872 a negative regulator of pho regulon [Pseudomonas aeruginosa] 60 37 645 159 3 778 1386 gnl|PID|e308090 product highly similar to Bacillus anthracis 60 48 609 CapA protein [Bacillus subtilis] 163 7 8049 8468 gnl|PID|d101313 YqeN [Bacillus subtilis] 60 38 420 170 3 4130 2688 gi|1574179 H. influenzae predicted coding region HI1244 60 39 1443 [Haemophilus influenzae] 171 7 4717 5901 gi|606076 ORF_o384 [Escherichia coli] 60 44 1185 183 3 2440 2135 gi|1877427 repressor [Streptococcus pyogenes phage T12] 60 38 306 191 10 9444 8428 gi|415664 catabolite control protein [Bacillus megaterium] 60 42 1017 200 1 139 1083 gi|438462 transmembrane protein [Bacillus subtilis] 60 37 945 201 3 3895 1928 gi|475112 enzyme IIabc [Pediococcus pentosaceus] 60 39 1968 214 15 10930 10439 gi|1573407 hypothetical [Haemophilus influenzae] 60 39 492 218 4 2145 2363 gi|608520 myosin heavy chain kinase A [Dictyostelium discoideum] 60 31 219 226 4 2518 2351 gi|437705 hyaluronidase [Streptococcus pneumoniae] 60 53 168 242 1 725 3 gi|43938 Sor regulator [Klebsiella pneumoniae] 60 41 723 245 1 1 288 gi|304897 EcoE type I restriction modification enzyme M subunit 60 56 288 [Escherichia coli] 251 1 905 45 gi|671632 unknown [Staphylococcus aureus] 60 36 861 259 1 969 82 gi|153794 rgg [Streptococcus gordonii] 60 32 888 260 2 1492 1662 pir|S31840|S318 probable transposase - Bacillus stearothermophilus 60 26 171 274 1 836 96 gi|1592173 N-ethylammeline chlorohydrolase [Methanococcus jannaschii] 60 40 741 308 1 463 2 gi|1787397 (AE000214) o157 [Escherichia coli] 60 43 462 318 1 3 308 gnl|PID|e137594 xerC recombinase [Lactobacillus leichmannii] 60 42 306 344 1 73 522 gi|509672 repressor protein [Bacteriophage Tuc2009] 60 32 450 5 1 576 4 gi|2293147 (AF008220) YtxM [Bacillus subtilis] 59 31 573 7 22 18140 17142 gnl|PID|e280724 unknown [Mycobacterium tuberculosis] 59 39 999 10 1 1413 4 gi|1353880 sialidase L [Macrobdella decora] 59 41 1410 15 6 6463 5156 gi|580841 F1 [Bacillus subtilis] 59 35 1308 22 2 479 1393 gi|142469 als operom regulatory protein [Bacillus subtilis] 59 34 915 22 5 2698 4614 gnl|PID|e280623 PCPA [Streptococcus pneumoniae] 59 44 1917 30 1 208 558 gnl|PID|e233868 hypothetical protein [Bacillus subtilis] 59 37 351 30 4 3678 2455 gnl|PID|e202290 unknown [Lactobacillus sake] 59 33 1224 35 13 12201 11071 gnl|PID|e238664 hypothetical protein [Bacillus subtilis] 59 35 1131 35 14 13288 12182 gi|1657647 Cap8H [Staphylococcus aureus] 59 39 1107 36 18 18076 17897 gi|1500535 M. jannaschii predicted coding region MJ1635 59 33 180 [Methanococcus jannaschii] 38 12 6172 7137 gi|2293239 (AF008220) YtxK [Bacillus subtilis] 59 34 966 42 3 1952 3361 gi|1684845 pinin [Canis familiaris] 59 40 1410 50 3 2678 1728 gnl|PID|d101329 YqjK [Bacillus subtilis] 59 41 951 56 5 1870 2388 gnl|PID|e137594 xerC recombinase [Lactobacillus leichmannii] 59 41 519 61 6 6812 5628 gnl|PID|e311516 aminotransferase [Bacillus subtilis] 59 40 1185 67 5 2382 3023 gi|1146190 2-keto-3-deoxy-6-phosphogluconate aldolase [Bacillus subtilis] 59 36 642 69 10 8567 8899 gi|1573628 antothenate kinase (coaA) [Haemophilus influenzae] 59 38 333 87 12 11383 10055 gnl|PID|e323504 putative Fmu protein [Bacillus subtilis] 59 44 1329 113 14 13927 15894 gi|1673731 (AE000010) Mycoplasma pneumoniae, fructose-permease 59 43 1968 IIBC component; similar to Swiss-Prot Accession Number P20966, from E. coli [Mycoplasma pneumoniae] 115 8 8766 8521 gi|1590886 M. jannaschii predicted coding region MJ0110 59 38 246 [Methanococcus jannaschii] 119 2 1966 1526 gnl|PID|e209005 homologous to ORF2 in nrdEF operons of 59 43 441 E. coli and S. typhimurium [ Lactococcus lactis] 128 17 13438 13178 gnl|PID|e279632 unknown [Mycobacterium tuberculosis] 59 38 261 140 22 23903 23388 gi|482922 protein with homology to pai1 repressor of 59 40 516 B. subtilis [Lactobacillus delbrueckii] 148 13 9697 9014 gnl|PID|d102005 (AB001488) FUNCTION UNKNOWN, SIMILAR 59 32 684 PRODUCT IN H. INFLUENZAE AND SYNECHOCYSTIS. [Bacillus subtilis] 149 10 7213 8244 gi|710422 cmp-binding-factor 1 [Staphylococcus aureus] 59 40 1032 164 9 6993 6013 gnl|PID|d100965 ferric anguibactin-binding protein precusor 59 41 981 FatB of V. anguillarum [ Bacillus subtilis] 164 12 8836 7823 gnl|PID|d100964 homologue of ferric anguibactin transport system 59 35 1014 permerase protein FatC of V. anguillarum [ Bacillus subtilis] 177 2 401 1072 gi|289759 coded for by C. elegans cDNA CE2G3 59 40 672 (GenBank: Z14728); putative [Caenorhabditis elegans] 177 7 3841 4200 gi|2313445 (AE000551) H. pylori predicted coding region 59 38 360 HP0342 [Helicobacter pylori] 183 4 2768 2508 gi|509672 repressor protein [Bacteriophage Tuc2009] 59 50 261 186 6 3398 2820 gi|606080 ORF_o290; Geneplot suggests frameshift 59 38 579 linking to o267, not found [Escherichia coli] 190 3 3120 1711 gi|1613768 histidine protein kinase [Streptococcus pneumoniae] 59 32 1410 194 2 1621 1019 gnl|PID|d100579 unknown [Bacillus subtilis] 59 40 603 198 7 5205 4306 gnl|PID|e313073 hypothetical protein [Bacillus subtilis] 59 38 900 220 5 4362 3958 gnl|PID|d101322 YqhL [Bacillus subtilis] 59 46 405 242 3 1573 2367 gi|1787045 (AE000184) f308; This 308 aa orf is 35 59 42 795 pct identical (35 gaps) to 305 residues of an approx. 296 aa protein PFLC_ECOLI SW: P32675 [Escherichia coli] 247 2 1154 1480 gi|40073 ORF107 [Bacillus subtilis] 59 39 327 256 1 868 2 gnl|PID|d101924 hemolysin [Synechocystis sp.] 59 39 867 258 1 65 820 gi|2246532 ORF 73, contains large complex repeat CR 73 [Kaposi's 59 20 756 sarcoma-associated herpesvirus] 270 1 386 1126 gnl|PID|d102092 YfnB [Bacillus subtilis] 59 40 741 281 1 552 166 gi|666062 putative [Lactococcus lactis] 59 31 387 309 1 3 479 gi|405879 yeiH [Escherichia coli] 59 38 477 363 1 2 1894 gi|915208 gastric mucin [Sus scrofa] 59 31 1893 387 2 425 84 gi|160671 S antigen precursor [Plasmodium falciparum] 59 44 342 5 6 11223 10465 gnl|PID|d101812 LumQ [Synechocystis sp.] 58 29 759 29 4 2098 3513 gnl|PID|d100479 Na+-ATPase subunit J [Enterococcus hirae] 58 39 1416 30 5 4058 3651 gi|39478 ATP binding protein of transport ATPases [Bacillus firmus] 58 34 408 33 6 2983 2210 gnl|PID|d101164 unknown [Bacillus subtilis] 58 45 774 36 8 5316 6179 gi|1518679 orf [Bacillus subtilis] 58 32 864 43 5 5926 3971 gi|1788150 (AE000278) protease II [Escherichia coli] 58 37 1956 46 5 3704 5221 gnl|PID|e267329 Unknown [Bacillus subtilis] 58 42 1518 48 14 11722 11066 gnl|PID|d101771 thiamin biosynthetic bifunctional enzyme [Synechocystis sp.] 58 34 657 52 1 1229 3 gnl|PID|d101291 reductase [Pseudomonas aeruginosa] 58 35 1227 53 2 702 412 gi|2313357 (AE000545) cytochrome c biogenesis protein (ccdA) 58 25 291 [Helicobacter pylori] 58 4 6586 5498 gi|147329 transport protein [Escherichia coli] 58 41 1089 69 5 4934 3807 gnl|PID|e311492 unknown [Bacillus subtilis] 58 41 1128 71 27 31357 32277 gi|2408014 hypothetical protein [Schizosaccharomyces pombe] 58 33 921 72 4 3586 2882 gi|18694 nodulin-21 (AA 1-201) [Glycine max] 58 34 705 74 3 4937 4230 gi|2293252 (AF008220) YtmO [Bacillus subtilis] 58 33 708 79 4 4594 3422 gi|1217989 ORF3 [Streptococcus pneumoniae] 58 44 1173 82 8 10585 8171 gi|882711 exonuclease V alpha-subunit [Escherichia coli] 58 38 2415 86 17 16017 15337 gi|47642 5-dehydroquinate hydrolyase (3-dehydroquinase) 58 32 681 [Salmonella typhi] 97 2 931 560 gi|153794 rgg [Streptococcus gordonii] 58 32 372 108 2 358 2724 gi|537020 vacB gene product [Escherichia coli] 58 37 2367 111 5 4593 5240 gi|1592142 ABC transporter, probable ATP-binding subunit 58 36 648 [Methanococcus jannaschii] 120 3 4421 5110 gnl|PID|d101320 YqgX [Bacillus subtilis] 58 47 690 128 16 13131 12673 gi|662919 ORF U [Enterococcus hirae] 58 42 459 132 3 6174 4939 gi|1800301 macrolide-efflux determinant [Streptococcus pneumoniae] 58 35 1236 133 1 111 890 gnl|PID|e269488 Unknown [Bacillus subtilis] 58 36 780 160 11 8615 9865 gi|473901 ORF1 [Lactococcus lactis] 58 39 1251 161 6 6268 6849 gnl|PID|d101024 DJ-1 protein [Homo sapiens] 58 32 582 169 1 214 2 gnl|PID|d100447 translation elongation factor-3 [Chlorella virus] 58 31 213 187 1 487 2 gi|475114 regulatory protein [Pediococcus pentosaceus] 58 38 486 187 6 4384 4620 gi|167475 dessication-related protein [Craterostigma plantagineum] 58 55 237 190 2 1464 1640 gnl|PID|e246727 competence pheromone [Streptococcus gordonii] 58 38 177 192 2 2012 1344 gnl|PID|d100556 rat GCP360 [Rattus rattus] 58 44 669 206 1 1292 696 gnl|PID|e202579 product similar to WrbA [Lactobacillus sake] 58 35 597 216 2 2333 555 gnl|PID|e325036 hypothetical protein [Bacillus subtilis] 58 33 1779 217 5 5250 4321 gi|466474 cellobiose phosphotransferase enzyme II” [Bacillus 58 38 930 stearothermophilus] 217 7 5636 5106 gnl|PID|d102048 B. subtilis cellobiose phosphotransferase 58 44 531 system celB; P46317 (998) transmembrane [Bacillus subtilis] 232 1 2 811 gi|1573777 cell division ATP-binding protein (ftsE) 58 39 810 [Haemophilus influenzae] 264 1 2 715 gi|973330 NatA [Bacillus subtilis] 58 32 714 280 1 33 767 gi|1786187 (AE000111) hypothetical 29.6 kD protein in thrC-talB 58 31 735 intergenic region [Escherichia coli] 306 1 845 3 gnl|PID|e334780 YlbL protein [Bacillus subtilis] 58 47 843 360 3 1556 1092 sp|P46351|YZGD_(—) HYPOTHETICAL 45.4 KD PROTEIN IN 58 32 465 THIAMINASE I 5′REGION. 363 5 2160 1867 gi|160671 S antigen precursor [Plasmodium falciparum] 58 51 294 372 1 806 3 gi|393394 Tb-291 membrane associated protein [Trypanosoma 58 37 804 brucei subgroup] 382 2 749 519 pir|JC1151|JC11 hypothetical 20.3K protein (insertion sequence IS1131) - 58 41 231 Agrobacterium tumefaciens (strain PO22) plasmid Ti 3 9 8409 7471 gi|1499745 M. jannaschii predicted coding region MJ0912 57 38 939 [Methanococcus jannaschii] 10 10 7674 7507 gi|1737169 homologue to SKP1 [Arabidopsis thaliana] 57 30 168 11 1 2 412 gnl|PID|d100139 ORF [Acetobacter pasteurianus] 57 42 411 31 4 2032 1388 gi|2293213 (AF008220) YtpR [Bacillus subtilis] 57 37 645 33 11 6931 6449 gnl|PID|e324949 hypothetical protein [Bacillus subtilis] 57 36 483 45 5 5446 5060 gi|1592204 phosphoserine phosphatase [Methanococcus jannaschii] 57 44 387 49 7 6523 7632 gi|155369 PTS enzyme-II fructose [Xanthomonas campestris] 57 35 1110 52 6 4520 6850 gi|1574144 single-stranded-DNA-specific exonuclease (recJ) 57 35 2331 [Haemophilus influenzae] 53 5 2079 1795 gi|1843580 replicase-associated polyprotein [oat blue dwarf virus] 57 46 285 63 6 5312 4995 gi|2182608 (AE000094) Y4rJ [Rhizobium sp. NGR234] 57 39 318 72 15 13883 13059 gnl|PID|d100892 homologous to SwissProt: YIDA_ECOLI hypothetical protein 57 40 825 [Bacillus subtilis] 79 2 2561 1815 gnl|PID|d100965 homologue of NADPH-flavin oxidoreductase Frp of V. harveyi 57 44 747 [Bacillus subtilis] 82 9 9596 9763 gi|1206045 short region of similarity to glycerophosphoryl diester 57 35 168 phosphodiesterases [Caenorhabditis elegans] 86 16 15371 14493 gi|1787983 (AE000264) o288; 92 pct identical (1 gaps) to 222 57 34 879 residues of fragment YDIB_ECOLI SW: P28244 (223 aa)[Escherichia coli] 93 3 1695 1177 gi|1500003 mutator mutT protein [Methanococcus jannaschii] 57 33 519 96 6 3026 4519 gi|559882 threonine synthase [Arabidopsis thaliana] 57 43 1494 99 14 17211 18212 gi|773349 BirA protein [Bacillus subtilis] 57 44 1002 112 8 7448 7903 gi|1591393 M. jannaschii predicted coding region MJ0678 57 30 456 [Methanococcus jannaschii] 113 16 18627 18328 pir|A45605|A456 mature-parasite-infected erythrocyte surface antigen MESA - 57 22 300 Plasmodium falciparum 123 2 343 1110 pir|F64149|F641 hypothetical protein HI0355 - Haemophilus influenzae 57 38 768 (strain Rd KW20) 123 4 2108 2884 gnl|PID|d102148 (AB001684) sulfate transport system permease protein 57 39 777 [Chlorella vulgaris] 127 10 6477 5587 gi|1573082 nitrogenase C (nifC) [Haemophilus influenzae] 57 35 891 128 13 9251 9790 gi|153692 pneumolysin [Streptococcus pneumoniae] 57 38 540 131 4 2139 1363 gi|42081 nagD gene product (AA 1-250) [Escherichia coli] 57 36 777 136 1 214 1221 bbs|148453 SpaA = endocarditis immunodominant antigen [Streptococcus 57 44 1008 sobrinus, MUCOB 263, Peptide, 1566 aa] [Streptococcus sobrinus] 140 25 28701 26851 gi|505576 beta-glucoside permease [Bacillus subtilis] 57 38 1851 141 6 6395 7438 gi|995560 unknown [Schizosaccharomyces pombe] 57 41 1044 144 3 3231 2785 gnl|PID|d100139 ORF [Acetobacter pasteurianus] 57 42 447 155 4 5454 4564 gi|600431 glycosyl transerase [Erwinia amylovora] 57 34 891 159 9 4877 5854 gi|290509 o307 [Escherichia coli] 57 35 978 167 11 9710 9249 gnl|PID|d100139 ORF [Acetobacter pasteurianus] 57 42 462 171 6 4023 4436 gi|147402 mannose permease subunit III-Man [Escherichia coli] 57 29 414 178 4 2170 1076 gnl|PID|d102004 (AB001488) ATP-DEPENDENT RNA HELICASE 57 39 1095 DEAD HOMOLOG. [Bacillus subtilis] 190 1 145 1455 gi|149420 export/processing protein [Lactococcus lactis] 57 30 1311 198 1 298 95 gi|522268 unidentified ORF22 [Bacteriophage bIL67] 57 36 204 203 2 3195 2110 gnl|PID|e283915 orf c01003 [Sulfolobus solfataricus] 57 41 1086 205 1 40 507 gi|1439527 EIIA-man [Lactobacillus curvatus] 57 28 468 214 7 4243 3797 gnl|PID|d102049 H. influenzae, ribosomal protein alanine 57 48 447 acetyltransferase; P44305 (189) [Bacillus subtilis] 268 3 1767 1276 gi|43979 L. curvatus small cryptic plasmid gene for rep protein 57 36 492 [Lactobacillus curvatus] 351 1 324 34 gnl|PID|e275871 T03F6.b [Caenorhabditis elegans] 57 31 291 386 1 226 2 gi|160671 S antigen precursor [Plasmodium falciparum] 57 45 225 5 5 10486 8777 gi|405857 yehU [Escherichia coli] 56 33 1710 8 5 3674 3910 gi|467199 pksC; L518_F1_2 [Mycobacterium leprae] 56 39 237 10 3 3442 1874 gnl|PID|d101907 sodium-coupled permease [Synechocystis sp.] 56 36 1569 21 1 1880 333 gi|2313949 (AE000593) osmoprotection protein (proWX) 56 33 1548 [Helicobacter pylori] 22 29 21968 22456 gnl|PID|d102001 (AB001488) PROBABLE ACETYLTRANSFERASE. 56 37 489 [Bacillus subtilis] 27 1 1361 3 gi|215132 ea59 (525) [Bacteriophage lambda] 56 30 1359 28 9 4667 4278 gi|1592090 DNA repair protein RAD2 [Methanococcus jannaschii] 56 29 390 33 1 3 386 gnl|PID|d100139 ORF [Acetobacter pasteurianus] 56 41 384 36 7 5122 5397 pir|PQ0053|PQ00 hypothetical protein (proC 3′ region) - pseudomonas 56 28 276 aeruginosa (strain PAO) (fragment) 40 4 3137 4318 gi|1800301 macrolide-efflux determinant [Streptococcus pneumoniae] 56 27 1182 40 16 12511 13191 gnl|PID|e217602 PlnU [Lactobacillus plantarum] 56 38 681 48 17 13775 13023 gi|143729 transcription activator [Bacillus subtilis] 56 35 753 75 4 1674 2594 gnl|PID|d102036 membrane protein [Bacillus stearothermophilus] 56 25 921 85 3 1842 1459 gnl|PID|d100139 ORF [Acetobacter pasteurianus] 56 41 384 89 7 5815 4940 gi|853777 product similar to E. coli PRFA2 protein [Bacillus subtilis] 56 42 876 105 2 1360 2718 gnl|PID|d101913 hypothetical protein [Synechocystis sp.] 56 37 1359 112 3 2151 3194 gi|537201 ORF_o345 [Escherichia coli] 56 31 1044 113 4 2754 2963 gnl|PID|d100340 ORF [Plum pox virus] 56 28 210 122 3 1203 2054 gi|1649035 high-affinity periplasmic glutamine binding protein [Salmonella 56 30 852 typhimurium] 124 8 3939 3694 gnl|PID|e248893 unknown [Mycobacterium tuberculosis] 56 27 246 125 4 4403 4107 gnl|PID|d100247 human non-muscle myosin heavy chain [Homo sapiens] 56 32 297 127 11 6608 6405 gi|2182397 (AE000073) Y4fN [Rhizobium sp. NGR234] 56 35 204 134 5 4769 3849 gnl|PID|d101870 hypothetical protein [Synechocystis sp.] 56 39 921 137 10 6814 7245 gi|1592011 sulfate permease (cysA) [Methanococcus jannaschii] 56 34 432 142 8 5019 4582 pir|A47071|A470 orf1 immediately 5′ of nifS - Bacillus subtilis 56 29 438 146 8 4676 3660 gnl|PID|d101911 hypothetical protein [Synechocystis sp.] 56 32 1017 148 3 1906 2739 gnl|PID|d101099 phosphate transport system permease protein PstA 56 36 834 [Synechocystis sp.] 150 4 4449 2743 gnl|PID|e304628 probably site-specific recombinase of the resolvase 56 27 1707 family of enzymes [Bacteriophage TP21] 172 1 2 208 gi|1787791 (AE000249) f317; This 317 aa orf is 27 pct 56 34 207 identical (16 gaps) to 301 residues of an approx. 320 aa protein YXXC_BACSU SW: P39140 [Escherichia coli] 172 7 4979 5668 gi|396293 similar to Bacillus subtilis hypoth. 20 kDa protein, 56 40 690 in tsr 3′ region [Escherichia coli] 186 7 3732 3367 gi|1732200 PTS permease for mannose subunit IIPMan [Vibrio furnissii] 56 36 366 187 2 2402 819 pir|S57904|S579 virR49 protein - Streptococcus pyogenes 56 35 1584 (strain CS101, serotype M49) 204 3 2772 2239 gi|606376 ORF_o162 [Escherichia coli] 56 35 534 206 3 3342 1633 gi|559861 clyM [Plasmid pAD1] 56 38 1710 219 3 1689 1096 gi|1146197 putative [Bacillus subtilis] 56 27 594 230 2 409 1485 pir|C60328|C603 hypothetical protein 2 (sr 5′ region) - Streptococcus 56 40 1077 mutans (strain OMZ175, serotype f) 233 4 2930 3268 gi|1041785 rhoptry protein [plasmodium yoelii] 56 24 339 273 2 1543 2724 gi|143089 iep protein [Bacillus subtilis] 56 32 1182 353 1 1 516 gnl|PID|e325000 hypothetical protein [Bacillus subtilis] 56 41 516 359 1 87 641 gi|1786952 (AE000176) o877; 100 pct identical to the first 86 56 46 555 residues of the 100 aa hypothetical protein fragment YBGB_ECOLI SW: P54746 [Escherichia coli] 363 7 4482 4198 gi|1573353 outer membrane integrity protein (tolA) 56 38 285 [Haemophilus influenzae] 376 1 2 508 gnl|PID|e325031 hypothetical protein [Bacillus subtilis] 56 33 507 18 1 836 177 gnl|PID|d100872 a negative regulator of pho regulon [Pseudomonas aeruginosa] 55 31 660 28 4 1824 1618 gnl|PID|e316518 STAT protein [Dictyostelium discoideum] 55 40 207 29 6 4496 5041 gi|1088261 unknown protein [Anabaena sp.] 55 31 546 38 16 9695 10702 gi|580905 B. subtilis genes rpmH, rnpA, 50 kd, gidA and gidB 55 31 1008 [Bacillus subtilis] 49 5 5727 6182 gi|1786951 (AE000176) heat-responsive regulatory protein 55 29 456 [Escherichia coli] 51 4 2381 3241 gnl|PID|d101293 YbbA [Bacillus subtilis] 55 42 861 52 9 9640 10866 gi|153016 ORF 419 protein [Staphylococcus aureus] 55 23 1227 53 4 1813 1349 gi|896042 OspF [Borrelia burgdorferi] 55 30 465 60 5 4794 5756 gi|1499876 magnesium and cobalt transport protein 55 38 963 [Methanococcus jannaschii] 71 9 14176 15408 gi|1857120 glycosyl transferase [Neisseria meningitidis] 55 41 1233 75 6 3189 4229 gnl|PID|e209890 NAD alcohol dehydrogenase [Bacillus subtilis] 55 44 1041 108 10 10488 9820 gnl|PID|e324997 hypothetical protein [Bacillus subtilis] 55 36 669 113 12 12273 13037 gnl|PID|e311496 unknown [Bacillus subtilis] 55 34 765 113 13 13007 13945 gi|1573423 1-phosphofructokinase (fruK) [Haemophilus influenzae] 55 39 939 126 5 6764 5907 gi|1790131 (AE000446) hypothetical 29.7 kD protein in ibpA-gyrB 55 37 858 intergenic region [Escherichia coli] 129 3 2719 902 gnl|PID|d101425 Pz-peptidase [Bacillus licheniformis] 55 35 1818 138 3 2593 1610 gi|142833 ORF2 [Bacillus subtilis] 55 37 984 140 6 6916 5633 gnl|PID|d100964 homologue of hypothetical protein in a rapamycin 55 26 1284 synthesis gene cluster of Streptomyces hygroscopicus [Bacillus subtilis] 147 3 3854 2136 gi|472330 dihydrolipoamide dehydrogenase [Clostridium magnum] 55 39 1719 147 10 10204 8921 gnl|PID|e73078 dihydroorotase [Lactobacillus leichmannii] 55 38 1284 148 5 3430 4119 gi|290572 peripheral membrane protein U [Escherichia coli] 55 29 690 148 6 4171 4650 gi|695769 transposase [Xanthobacter autotrophicus] 55 37 480 149 14 12564 11650 gnl|PID|d101329 YqjG [Bacillus subtilis] 55 32 915 156 3 1113 550 gi|2314496 (AE000634) conserved hypothetical integral membrane 55 34 564 protein [Helicobacter pylori] 159 10 6625 5897 gi|290533 similar to E. coli ORF adjacent to suc operon; 55 29 729 similar to gntR class of regulatory proteins [Escherichia coli] 164 3 1784 2332 gnl|PID|e255118 hypothetical protein [Bacillus subtilis] 55 37 549 164 5 2772 3521 gi|40348 put. resolvase Tnp I (AA 1-284) [Bacillus thuringiensis] 55 35 750 164 11 7428 7216 gnl|PID|e249407 unknown [Mycobacterium tuberculosis] 55 38 213 167 5 3860 3345 gi|535052 involved in protein secretion [Bacillus subtilis] 55 28 516 186 5 2880 2563 gi|606080 ORF_o290; Geneplot suggests frameshift linking 55 35 318 to o267, not found [Escherichia coli] 189 8 4311 5396 gnl|PID|e183450 hypothetical EcsB protein [Bacillus subtilis] 55 32 1086 192 5 3270 3079 gi|1196504 vitellogenin convertase [Aedes aegypti] 55 38 192 195 2 2454 1384 gi|1574693 transferase, peptidoglycan synthesis (murG) 55 33 1071 [Haemophilus influenzae] 198 4 3013 2471 gnl|PID|e313074 hypothetical protein [Bacillus subtilis] 55 29 543 214 1 373 744 gnl|PID|d101741 transposase [Synechocystis sp.] 55 33 372 219 2 1115 456 gi|288301 ORF2 gene product [Bacillus megaterium] 55 30 660 263 7 3742 3443 gi|18137 cgcr-4 product [Chlamydomonas reinhardtii] 55 48 300 285 1 2 829 gnl|PID|d100974 unknown [Bacillus subtilis] 55 40 828 286 1 650 249 gi|396844 ORF (18 kDa) [Vibrio cholerae] 55 31 402 297 2 1229 1696 gi|150848 prtC [Porphyromonas gingivalis] 55 39 468 309 2 218 982 gi|1574491 hypothetical [Haemophilus influenzae] 55 35 765 328 2 646 224 gi|571500 prohibitin [Saccharomyces cerevisiae] 55 27 423 330 1 1340 474 gi|396397 soxS [Escherichia coli] 55 29 867 364 3 2538 1546 gi|393394 Tb-291 membrane associated protein [Trypanosoma brucei 55 36 993 subgroup] 368 3 941 105 gi|160671 S antigen precursor [Plasmodium falciparum] 55 40 837 3 5 4604 3624 gi|2293176 (AF008220) signal transduction protein kinase [Bacillus subtilis] 54 26 981 9 11 7746 7246 gi|1146245 putative [Bacillus subtilis] 54 38 501 38 24 16213 17937 gi|1480429 putative transcriptional regulator [Bacillus stearothermophilus] 54 27 1725 40 8 5076 4882 gi|39989 methionyl-tRNA synthetase [Bacillus stearothermophilus] 54 35 195 43 4 3980 2367 gnl|PID|e148611 ABC transporter [Lactobacillus helveticus] 54 25 1614 52 10 10844 12103 gi|1762962 FemA [Staphylococcus simulans] 54 29 1260 57 1 3 512 gi|558177 endo-1,4-beta-xylanase [Cellulomonas fimi] 54 36 510 58 3 4749 4246 gnl|PID|d101237 hypothetical [Bacillus subtilis] 54 29 504 71 7 10684 11703 gi|510255 orf3 [Escherichia coli] 54 31 1020 71 20 27546 27737 gi|202543 serotonin receptor [Rattus norvegicus] 54 31 192 72 2 844 1098 gi|148613 srnB gene product [Plasmid F] 54 37 255 72 7 7438 6695 gi|1196496 recombinase [Moraxella bovis] 54 38 744 74 10 14043 13465 gi|1200342 ORF 3 gene product [Bradyrhizobium japonicum] 54 32 579 74 12 16483 15995 gi|2317798 maturase-related protein [Pseudomonas alcaligenes] 54 30 489 86 3 2877 2155 gi|46988 orf9.6 possibly encodes the O unit polymerase 54 34 723 [Salmonella enterica] 89 5 4433 3921 gi|147211 phnO protein [Escherichia coli] 54 41 513 90 1 3 464 gi|2317798 maturase-related protein [Pseudomonas alcaligenes] 54 30 462 96 10 8058 8510 gnl|PID|d102015 (AB001488) SIMILAR TO SALMONELLA TYPHIMURIUM 54 32 453 SLYY GENE REQUIRED FOR SURVIVAL IN MACROPHAGE. [Bacillus subtilis] 97 6 4662 3604 gi|1591394 transketolase” [Methanococcus jannaschii] 54 30 1059 106 11 10406 12010 gi|606286 ORF_o637 [Escherichia coli] 54 32 1605 147 8 8663 7404 gnl|PID|d101615 ORF_ID: o319#7; similar to [SwissProt Accession Number 54 35 1260 P37340] [Escherichia coli] 171 4 2477 3223 gi|1439528 EIIC-man [Lactobacillus curvatus] 54 36 747 174 2 2068 1787 gnl|PID|d100518 motor protein [Homo sapiens] 54 35 282 188 1 526 1188 gnl|PID|e250352 unknown [Mycobacterium tuberculosis] 54 31 663 198 5 3582 2884 gnl|PID|e313074 hypothetical protein [Bacillus subtilis] 54 33 699 207 1 1 1641 gnl|PID|d101813 hypothetical protein [Synechocystis sp.] 54 24 1641 210 1 2 655 gi|2293206 (AF008220) YtmP [Bacillus subtilis] 54 29 654 225 2 966 2357 gnl|PID|e330194 R11H6.1 [Caenorhabditis elegans] 54 39 1392 241 1 1681 347 gnl|PID|d101813 hypothetical protein [Synechocystis sp.] 54 26 1335 263 2 907 1395 gnl|PID|d101886 transposase [Synechocystis sp.] 54 30 489 263 6 3450 2977 gi|160671 S antigen precursor [Plasmodium falciparum] 54 47 474 277 3 2517 1363 gi|1196926 unknown protein [Streptococcus mutans] 54 30 1155 307 1 828 4 gi|2293198 (AF008220) YtgP [Bacillus subtilis] 54 28 825 325 1 19 768 gi|2182507 (AE000083) Y4lH [Rhizobium sp. NGR234] 54 37 750 332 2 898 590 gi|1591815 ADP-ribosylglycohydrolase (draG) [Methanococcus jannaschii] 54 32 309 385 4 240 479 gi|530878 amino acid feature: N-glycosylation sites, aa 41 . . . 43, 54 49 240 46 . . . 48, 51 . . . 53, 72 . . . 74, 107 . . . 109, 128 . . . 130, 132 . . . 134, 158 . . . 160, 163 . . . 165; amino acid feature: Rod protein domain, aa 169 . . . 340; amino acid feature: globular protein domai 7 25 19702 19493 gnl|PID|e255111 hypothetical protein [Bacillus subtilis] 53 32 210 23 3 2497 2033 gnl|PID|d102015 (AB001488) SIMILAR TO SALMONELLA TYPHIMURIUM 53 25 465 SLYY GENE REQUIRED FOR SURVIVAL IN MACROPHAGE. [Bacillus subtilis] 29 11 9042 10121 gi|143331 alkaline phosphatase regulatory protein [Bacillus subtilis] 53 31 1080 33 3 1479 1009 pir|S10655|S106 hypothetical protein X - Pyrococcus woesei (fragment) 53 33 471 36 6 4583 5134 gnl|PID|e316029 unknown [Mycobacterium tuberculosis] 53 30 552 38 14 8521 8898 gi|580904 homologous to E. coli rnpA [Bacillus subtilis] 53 30 378 52 7 7007 8686 gi|1377831 unknown [Bacillus subtilis] 53 29 1680 54 17 17555 19564 gi|666069 orf2 gene product [Lactobacillus leichmannii] 53 36 2010 56 1 1 681 gi|1592266 restriction modification system S subunit 53 32 681 [Methanococcus jannaschii] 57 10 9431 8487 gi|1788543 (AE000310) f351; Residues 1-121 are 100 pct identical to 53 31 945 YOJL_ECOLI SW: P33944 (122 aa) and aa 152-351 are 100 pct identical to YOJK_ECOLI SW: P33943 [Escherichia coli] 61 1 429 4 gnl|PID|e236467 B0024.12 [Caenorhabditis elegans] 53 33 426 71 1 5772 4 gi|393394 Tb-291 membrane associated protein [Trypanosoma brucei 53 33 5769 subgroup] 72 3 894 2840 gi|2293178 (AF008220) YtsD [Bacillus subtilis] 53 27 1947 73 14 9793 9212 gi|1778556 putative cobalamin synthesis protein [Escherichia coli] 53 32 582 88 7 5217 4342 gi|2098719 putative fimbrial-associated protein [Actinomyces naeslundii] 53 38 876 93 5 2395 1688 gi|563366 gluconate oxidoreductase [Gluconobacter oxydans] 53 33 708 96 9 6632 7762 gi|517204 ORF1, putative 42 kDa protein [Streptococcus pyogenes] 53 42 1131 108 8 7629 8600 gi|149581 maturation protein [Lactobacillus paracasei] 53 32 972 128 9 6412 6972 gnl|PID|e317237 unknown [Mycobacterium tuberculosis] 53 36 561 128 12 8429 9253 gi|311070 pentraxin fusion protein [Xenopus laevis] 53 31 825 148 1 3 950 pir|A61607|A616 probable hemolysin precursor - Streptococcus agalactiae 53 36 948 (strain 74-360) 163 2 2162 3022 gi|1755150 nocturnin [Xenopus laevis] 53 30 861 171 3 2304 2624 gi|1732200 PTS permease for mannose subunit IIPMan [Vibrio furnissii] 53 32 321 182 5 3785 3051 gnl|PID|d100572 unknown [Bacillus subtilis] 53 35 735 209 3 2948 1935 gi|1778505 ferric enterobactin transport protein [Escherichia coli] 53 28 1014 218 5 3884 2406 gi|40162 murE gene product [Bacillus subtilis] 53 34 1479 250 3 473 790 gnl|PID|e334776 YlbH protein [Bacillus subtilis] 53 30 318 275 1 1 1611 gnl|PID|d101314 YqeW [Bacillus subtilis] 53 35 1611 332 1 544 2 gi|409286 bmrU [Bacillus subtilis] 53 31 543 2 2 2543 3445 gnl|PID|e233879 hypothetical protein [Bacillus subtilis] 52 39 903 3 22 22402 23376 gi|38969 lacF gene product [Agrobacterium radiobacter] 52 36 975 5 3 8094 2356 gnl|PID|e324915 IgA1 protease [Streptococcus sanguis] 52 32 5739 22 26 19961 20212 gi|152901 ORF 3 [Spirochaeta aurantia] 52 35 252 22 31 23140 24666 gi|289262 comE ORF3 [Bacillus subtilis] 52 32 1527 27 6 5397 4801 gi|39573 P20 (AA 1-178) [Bacillus licheniformis] 52 35 597 35 10 8604 7357 gi|508241 putative O-antigen transporter [Escherichia coli] 52 27 1248 45 4 4801 3662 gnl|PID|d102243 (AB005554) homologs are found in E. coli and H. influenzae; 52 36 1140 see SWISS_PROT ACC#: P42100 [Bacillus subtilis] 48 18 14385 13726 gnl|PID|e205174 orf2 [Lactobacillus helveticus] 52 25 660 49 4 5321 5755 gi|2317740 (AF013987) nitrogen regulatory IIA protein [Vibrio cholerae] 52 19 435 54 4 2773 4668 gi|1500472 M. jannaschii predicted coding region MJ1577 52 36 1896 [Methanococcus jannaschii] 54 6 5250 4969 gi|2182453 (AE000079) Y4iO [Rhizobium sp. NGR234] 52 40 282 66 6 8400 6955 gi|43140 TrkG protein [Escherichia coli] 52 30 1446 71 26 30659 31312 gnl|PID|e314993 unknown [Mycobacterium tuberculosis] 52 23 654 75 2 1673 1035 gnl|PID|d102271 (AB001683) FarA [Streptomyces sp.] 52 27 639 81 3 1439 2893 gnl|PID|e311458 rhamnulose kinase [Bacillus subtilis] 52 32 1455 81 8 4987 5781 gi|147403 mannose permease subunit II-P-Man [Escherichia coli] 52 37 795 83 21 20687 21853 gi|143365 phosphoribosyl aminoimidazole carboxylase II 52 37 1167 (PUR-K; ttg start codon) [Bacillus subtilis] 86 6 5785 4592 gi|1276879 EpsF [Streptococcus thermophilus] 52 26 1194 86 20 19390 17861 gi|454844 ORF 3 [Schistosoma mansoni] 52 26 1530 96 13 10540 9659 gi|288299 ORF1 gene product [Bacillus megaterium] 52 33 882 111 1 2 2026 gi|148309 cytolysin B transport protein [Enterococcus faecalis] 52 27 2025 112 2 1457 2167 gi|471234 orf1 [Haemophilus influenzae] 52 33 711 118 3 2931 2365 bbs|151233 Mip = 24 kda macrophage infectivity potentiator 52 33 567 protein [Legionella pneumophila, Philadelphia-1, Peptide, 184 aa] [Legionella pneumophila] 122 9 5646 5951 gi|8214 myosin heavy chain [Drosophila melanogaster] 52 36 306 122 11 6159 6374 gi|434025 dihydrolipoamide acetyltransferase [Pelobacter carbinolicus] 52 52 216 134 6 4880 6313 gi|153733 M protein trans-acting positive regulator 52 43 1434 [Streptococcus pyogenes] 135 3 1238 2716 gnl|PID|e245024 unknown [Mycobacterium tuberculosis] 52 35 1479 141 3 1681 2319 gnl|PID|d100573 unknown [Bacillus subtilis] 52 32 6391 161 4 2562 5024 gi|1146243 22.4% identity with Escherichia coli DNA-damage 52 36 2463 inducible protein . . . ; putative [Bacillus subtilis] 173 2 968 183 gi|1215693 putative orf; GT9_orf434 [Mycoplasma pneumoniae] 52 30 786 198 6 4400 3567 gnl|PID|e313010 hypothetical protein [Bacillus subtilis] 52 26 834 210 12 8844 9107 gi|497647 DNA gyrase subunit B [Mycoplasma genitalium] 52 38 264 214 10 5264 5431 gi|550697 envelope protein [Human immunodeficiency virus type 1] 52 36 168 225 1 15 884 gi|1552773 hypothetical [Escherichia coli] 52 34 870 230 1 39 362 gnl|PID|d100582 unknown [Bacillus subtilis] 52 28 324 287 1 871 2 gnl|PID|e335028 protease/peptidase [Mycobacterium leprae] 52 29 870 363 2 1305 4 gi|393394 Tb-291 membrane associated protein 52 32 1302 [Trypanosoma brucei subgroup] 23 2 2048 1173 gnl|PID|e254943 unknown [Mycobacterium tuberculosis] 51 30 876 29 3 742 1521 gi|929900 5′-methylthioadenosine phosphorylase [Sulfolobus solfataricus] 51 31 780 45 1 410 1597 gi|1877429 integrase [Streptococcus pyogenes phage T12] 51 32 1188 48 26 19227 18946 gi|2314455 (AE000633) transcriptional regulator (tenA) 51 33 282 [Helicobacter pylori] 73 5 4276 4016 gi|474177 alpha-D-1,4-glucosidase [Staphylococcus xylosus] 51 31 261 81 11 8935 12057 gi|311070 pentraxin fusion protein [Xenopus laevis] 51 31 3123 83 5 1195 1986 gnl|PID|d101316 YqfI [Bacillus subtilis] 51 33 7921 98 10 7531 8538 gi|41500 ORF 3 (AA 1-352); 38 kD (put. ftsX) [Escherichia coli] 51 28 1008 113 6 3908 5173 gi|466882 pps1; B1496_C2_189 [Mycobacterium leprae] 51 27 1266 124 1 326 57 gi|2191168 (AF007270) contains similarity to myosin heavy chain 51 32 270 [Arabidopsis thaliana] 129 10 7286 6816 gi|1046241 orf14 [Bacteriophage HP1] 51 30 471 143 3 4963 3983 gi|1354935 probable copper-transporting atpase [Escherichia coli] 51 26 981 148 15 11359 10226 gi|2293256 (AF008220) putative hippurate hydrolase [Bacillus subtilis] 51 36 1134 149 8 6003 7313 gi|1633572 Herpesvirus saimiri ORF73 homolog [Kaposi's 51 21 1311 sarcoma-associated herpes-like virus] 151 9 12092 11550 gnl|PID|e281580 hypothetical 40.7 kd protein [Bacillus subtilis] 51 34 543 159 6 2555 3208 gi|146944 CMP-N-acetylneuraminic acid synthetase [Escherichia coli] 51 36 654 174 1 1797 4 gi|1773166 probable copper-transporting atpase [Escherichia coli] 51 28 1794 265 4 2231 1773 gnl|PID|e256400 anti-P. falciparum antigenic polypeptide [Saimiri sciureus] 51 18 459 277 2 643 1311 pir|S32915|S329 pilD protein - Neisseria gonorrhoeae 51 33 669 350 1 890 3 gi|290509 o307 [Escherichia coli] 51 30 888 363 4 1228 4485 gi|1707247 partial CDS [Caenorhabditis elegans] 51 23 3258 367 1 1701 4 gi|393394 Tb-291 membrane associated protein 51 32 1698 [Trypanosoma brucei subgroup] 15 5 5174 4497 gnl|PID|e58151 F3 [Bacillus subtilis] 50 38 678 16 4 2220 2582 gnl|PID|e325010 hypothetical protein [Bacillus subtilis] 50 29 363 19 5 2591 4159 gi|1552733 similar to voltage-gated chloride channel protein 50 30 1569 [Escherichia coli] 25 4 2701 1997 gi|887849 ORF_f219 [Escherichia coli] 50 27 705 35 1 211 417 gnl|PID|e236697 unknown [Saccharomyces cerevisiae] 50 33 207 39 4 3416 5152 gnl|PID|d100974 unknown [Bacillus subtilis] 50 27 1737 51 7 4000 5181 gi|1592027 carbamoyl-phosphate synthase, pyrimidine-specific, 50 27 1182 large subunit [Methanococcus jannaschii] 51 9 7179 8303 gi|1591847 type I restriction-modification enzyme, 50 28 1125 S subunit [Methanococcus jannaschii] 52 8 8740 9534 gi|144297 acetyl esterase (XynC) [Caldocellum saccharolyticum] 50 34 795 52 16 16591 15770 gi|2108229 basic surface protein [Lactobacillus fermentum] 50 34 822 57 7 6031 6336 gi|2275264 60S ribosomal protein L7B [Schizosaccharomyces pombe] 50 40 306 71 23 29348 28383 gnl|PID|d101328 YqjA [Bacillus subtilis] 50 30 966 86 12 11155 10769 gnl|PID|e324964 hypothetical protein [Bacillus subtilis] 50 24 387 93 2 1205 330 gi|1066016 similar to Escherichia coli pyruvate, water dikinase, 50 24 876 Swiss-Prot Accession Number P23538 [Pyrococcus furiosus] 96 5 1673 2959 gnl|PID|e322433 gamma-glutamylcysteine synthetase [Brassica juncea] 50 29 1287 98 2 218 1171 gi|151110 leucine-, isoleucine-, and valine-binding protein 50 30 954 [Pseudomonas aeruginosa] 103 4 3303 2785 gi|154330 O-antigen ligase [Salmonella typhimurium] 50 31 519 115 5 6480 5980 gi|895747 putative cel operon regulator [Bacillus subtilis] 50 26 501 129 11 7559 7305 gi|1216475 skeletal muscle ryanodine receptor [Homo sapiens] 50 32 255 129 13 8192 7965 gi|152271 319-kDA protein [Rhizobium meliloti] 50 30 228 151 5 7634 6819 gi|40348 put. resolvase Tnp I (AA 1-284) [Bacillus thuringiensis] 50 35 816 153 1 1 597 gnl|PID|d102015 (AB001488) SIMILAR TO NITROREDUCTASE. 50 29 597 [Bacillus subtilis] 155 5 5986 5432 gi|1276880 EpsG [Streptococcus thermophilus] 50 28 555 160 9 7390 6323 gi|1786983 (AE000179) o331; 92 pct identical to the 333 aa 50 30 1068 hypothetical protein YBHE_ECOLI SW: P52697; 26 pct identical (7 gaps) to 167 residues of the 373 aa protein MLE_TRICU SW: P46057; SW: P52697 [Escherichia coli] 163 6 7396 8091 gnl|PID|d101313 YqeN [Bacillus subtilis] 50 22 696 167 6 5232 3940 gi|413926 ipa-2r gene product [Bacillus subtilis] 50 27 1293 169 2 807 130 gnl|PID|e304540 endolysin [Bacteriophage Bastille] 50 35 678 171 5 3168 4025 gi|606080 ORF_o290; Geneplot suggests frameshift linking 50 27 858 to o267, not found [Escherichia coli] 210 11 8151 8414 gi|330038 HRV 2 polyprotein [Human rhinovirus] 50 25 264 364 1 1538 135 gi|393396 Tb-292 membrane associated protein 50 31 1404 [Trypanosoma brucei subgroup] 10 7 5911 5090 gi|144859 ORF B [Clostridium perfringens] 49 24 822 26 5 10754 9768 gi|142440 ATP-dependent nuclease [Bacillus subtilis] 49 31 987 66 7 9777 8398 gi|414170 trkA gene product [Methanosarcina mazeii] 49 26 1380 77 6 5364 4648 gnl|PID|e285322 RecX protein [Mycobacterium smegmatis] 49 28 717 82 13 12689 13249 gnl|PID|e255091 hypothetical protein [Bacillus subtilis] 49 20 561 93 9 4866 4531 gi|40067 X gene product [Bacillus sphaericus] 49 26 336 112 5 4019 4948 gi|1574380 lic-1 operon protein (licB) [Haemophilus influenzae] 49 27 930 129 7 6058 4949 gnl|PID|e267587 Unknown [Bacillus subtilis] 49 35 1110 135 5 3875 4438 gi|39573 P20 (AA 1-178) [Bacillus licheniformis] 49 25 564 154 2 1423 1953 gnl|PID|d101102 regulatory components of sensory transduction system 49 29 531 [Synechocystis sp.] 156 5 2878 1637 gnl|PID|d101732 hypothetical protein [Synechocystis sp.] 49 25 1242 173 5 3500 2940 gi|490324 LORF X gene product [unidentified] 49 30 561 182 1 1057 2 gi|331002 first methionine codon in the ECLF1 ORF 49 25 1056 [Saimiriine herpesvirus 2] 192 6 5352 3667 gi|2394472 (AF024499) contains similarity to homeobox domains 49 23 1686 [Caenorhabditis elegans] 253 4 1129 1350 gi|531116 SIR4 protein [Saccharomyces cerevisiae] 49 23 222 277 1 600 136 gi|396844 ORF (18 kDa) [Vibrio cholerae] 49 32 465 327 3 1435 887 gi|733524 phosphatidylinositol-4,5-diphosphate 3-kinase 49 24 549 [Dictyostelium discoideum] 365 3 1436 132 gi|393394 Tb-291 membrane associated protein 49 31 1305 [Trypanosoma brucei subgroup] 33 7 4461 3277 gi|145644 codes for a protein of unknown function [Escherichia coli] 48 26 1185 40 2 652 1776 gnl|PID|e290649 ornithine decarboxylase [Nicotiana tabacum] 48 29 1125 67 4 1377 2384 gi|1772652 2-keto-3-deoxygluconate kinase [Haloferax alicantei] 48 30 1008 74 2 4269 3871 gi|2182678 (AE000101) Y4vJ [Rhizobium sp. NGR234] 48 27 399 81 2 1326 541 gi|153672 lactose repressor [Streptococcus mutans] 48 33 786 81 4 2981 3646 gi|146042 fuculose-1-phosphate aldolase (fucA) [Escherichia coli] 48 30 666 97 1 602 51 gi|153794 rgg [Streptococcus gordonii] 48 29 552 110 1 1 3132 gi|1381114 prtB gene product [Lactobacillus delbrueckii] 48 23 3132 131 5 2914 2147 gnl|PID|e183811 Acyl-ACP thioesterase [Brassica napus] 48 27 768 133 4 3494 2628 gnl|PID|e261988 putative ORF [Bacillus subtilis] 48 27 867 139 6 4231 4599 gi|1049388 ZK470.1 gene product [Caenorhabditis elegans] 48 23 369 139 8 5036 5665 gi|1022725 unknown [Staphylococcus haemolyticus] 48 29 630 140 12 11936 11007 gnl|PID|d102049 H. influenzae, ribosomal protein alanine 48 27 930 acetyltransferase; P44305 (189) [Bacillus subtilis] 146 9 5670 4654 gi|1591731 melvalonate kinase [Methanococcus jannaschii] 48 24 1017 161 3 1280 2374 gnl|PID|d101578 Collagenase precursor (EC 3.4.—.—). [Escherichia coli] 48 24 1095 172 11 10581 11048 gnl|PID|d101132 hypothetical protein [Synechocystis sp.] 48 27 468 182 4 2930 2586 gi|40067 X gene product [Bacillus sphaericus] 48 37 345 210 15 10786 11196 sp|P13940|LE29_(—) LATE EMBRYOGENESIS ABUNDANT 48 30 411 PROTEIN D-29 (LEA D-29). 214 12 6231 6482 gi|40389 non-toxic components [Clostridium botulinum] 48 26 252 221 1 704 3 gi|1573364 H. influenzae predicted coding region HI0392 48 27 702 [Haemophilus influenzae] 227 2 647 3928 gi|1673693 (AE000005) Mycoplasma pneumoniae, C09_orf718 48 30 3282 Protein [Mycoplasma pneumoniae] 253 2 480 758 gnl|PID|e236697 unknown [Saccharomyces cerevisiae] 48 31 279 363 3 1874 1122 gi|18137 cgcr-4 product [Chlamydomonas reinhardtii] 48 40 753 389 1 505 2 gi|18137 cgcr-4 product [Chlamydomonas reinhardtii] 48 38 504 3 21 20879 22258 gnl|PID|e264778 putative maltose-binding pootein [Streptomyces coelicolor] 47 33 1380 6 4 4089 4658 gi|39573 P20 (AA 1-178) [Bacillus licheniformis] 47 23 570 15 3 3736 1760 gnl|PID|d100572 unknown [Bacillus subtilis] 47 25 1977 35 15 14516 13263 gi|1773351 Cap5L [Staphylococcus aureus] 47 20 1254 51 6 3547 4002 pir|A37024|A370 32K antigen precursor - Mycobacterium tuberculosis 47 38 456 55 8 10154 9273 gi|39848 U3 [Bacillus subtilis] 47 26 882 92 4 1753 3276 gnl|PID|e280611 PCPC [Streptococcus pneumoniae] 47 35 1524 127 9 5589 5386 gi|1786458 (AE000134) f120; This 120 aa orf is 76 pct identical 47 32 204 (0 gaps) to 42 residues of an approx. 48 aa protein Y127_HAEIN SW: P43949 [Escherichia coli] 130 2 1232 1759 gnl|PID|e266555 unknown [Mycobacterium tuberculosis] 47 23 528 140 4 4951 3542 gnl|PID|d100964 homologue of hypothetical protein in a rapamycin synthesis gene 47 24 1410 cluster of Streptomyces hygroscopicus [Bacillus subtilis] 151 4 6814 6200 gi|1522674 M. jannaschii predicted coding region MJECL41 47 27 615 [Methanococcus jannaschii] 157 3 803 1174 gnl|PID|d101320 YqgZ [Bacillus subtilis] 47 25 372 178 5 3267 2155 gi|2367190 (AE000390) o334; sequence change joins ORFs ygjR & ygjS 47 30 1113 from earlier version (YGJR_ECOLI SW: P42599 and YGJS_ECOLI SW: P42600) [Escherichia coli] 273 1 2 1549 gnl|PID|e254973 autolysin sensor kinase [Bacillus subtilis] 47 32 1548 300 2 880 644 gi|1835755 zinc finger protein Png-1 [Mus musculus] 47 22 237 54 14 14182 12638 pir|S43609|S436 rofA protein - Streptococcus pyogenes 46 24 1545 88 1 2 1018 gnl|PID|e223891 xylose repressor [Anaerocellum thermophilum] 46 27 1017 96 7 4553 5860 gnl|PID|d101652 ORF_ID: o347#5; similar to [SwissProt Accession 46 23 1308 Number P45272] [Escherichia coli] 112 1 1127 3 gi|2209215 (AF004325) putative oligosaccharide repeat unit transporter 46 24 1125 [Streptococcus pneumoniae] 122 13 7308 7982 gi|1054776 hr44 gene product [Homo sapiens] 46 34 675 127 14 9198 8125 gi|1469286 afuA gene product [Actinobacillus pleuropneumoniae] 46 28 1074 132 4 7093 6197 gi|153794 rgg [Streptococcus gordonii] 46 26 897 140 8 8220 7723 gi|1235795 pullulanase [Thermoanaerobacterium thermosulfurigenes] 46 21 498 140 9 9205 8315 gi|407878 leucine rich protein [Streptococcus equisimilis] 46 27 891 162 1 1 1125 gi|1143209 ORF7; Method: conceptual translation supplied by author 46 25 1125 [Shigella sonnei] 199 1 1 585 gi|1947171 (AF000299) No definition line found [Caenorhabditis elegans] 46 28 585 223 3 1971 1477 sp|P02562|MYSS_(—) MYOSIN HEAVY CHAIN, SKELETAL 46 27 495 MUSCLE (FRAGMENTS). 232 2 760 1608 gi|1016112 ycf38 gene product [Cyanophora paradoxa] 46 28 849 292 1 687 220 gi|1673744 (AE000011) Mycoplasma pneumoniae, cytidine deaminase; 46 29 468 similar to GenBank Accession Number C53312, from M. pirum [Mycoplasma pneumoniae] 30 8 5843 6472 gi|1788049 (AE000270) o235; This 235 aa orf is 29 pct identical 45 24 630 (10 gaps) to 198 residues of an approx. 216 aa protein YTXB_BACSU SW: P06568 [Escherichia coli] 48 6 3461 3868 gi|722339 unknown [Acetobacter xylinum] 45 29 408 60 1 307 2 gi|1699079 coded for by C. elegans cDNA yk41h4.3; coded for by 45 36 306 C. elegans cDNA yk148g10.5; coded for by C. elegans cDNA yk152g5.5; coded for by C. elegans cDNA yk59a10.5; coded for by C. elegans cDNA yk41h4.5; coded for by C. elegans cDNA cm20g10; coded 72 16 14371 14874 gi|1321900 NADH dehydrogenase (ubiquinone) [Artemia franciscana] 45 25 504 99 7 9158 7941 gi|152192 mutation causes a succinoglucan-minus phenotype; 45 28 1218 ExoQ is atransmembrane protein; third gene of the exoYFQ operon;; putative [Rhizobium meliloti] 127 12 7046 6606 bbs|153689 HitB = iron utilization protein [Haemophilus influenzae, 45 24 441 type b, DL42, NTHI TN106, Peptide, 506 aa] [Haemophilus influenzae] 137 5 1561 2619 gi|472921 v-type Na-ATPase [Enterococcus hirae] 45 33 1059 209 1 774 364 gi|304141 restriction endonuclease beta subunit [Bacillus coagulans] 45 28 411 314 1 604 2 gi|1480457 latex allergen [Hevea brasiliensis] 45 31 603 20 18 19782 20288 gi|433942 ORF [Lactococcus lactis] 44 26 507 87 8 7030 6452 gi|537207 ORF_f277 [Escherichia coli] 44 26 579 166 5 4909 4037 gnl|PID|e308082 membrane transport protein [Bacillus subtilis] 44 25 873 247 1 818 75 gnl|PID|d100718 ORF1 [Bacillus sp.] 44 20 744 32 3 1885 3876 gi|2351768 PspA [Streptococcus pneumoniae] 43 24 1992 36 17 15467 18256 gi|1045739 M. genitalium predicted coding region 43 26 2790 MG064 [Mycoplasma genitalium] 54 15 14656 17343 gi|520541 penicillin-binding proteins 1A and 1B [Bacillus subtilis] 43 27 2688 67 2 696 1352 gi|536934 yjcA gene product [Escherichia coli] 43 29 657 139 2 2416 338 gi|396400 similar to eukaryotic Na+/H+ exchangers [Escherichia coli] 43 24 2079 298 1 3 809 gi|413972 ipa-48r gene product [Bacillus subtilis] 43 24 807 387 1 47 427 gi|2315652 (AF016669) No definition line found [Caenorhabditis elegans] 43 30 381 185 4 4221 3127 gi|2182399 (AE000073) Y4fP [Rhizobium sp. NGR234] 41 25 1095 340 1 582 70 gnl|PID|e218681 CDP-diacylglycerol synthetase [Arabidopsis thaliana] 41 20 513 363 6 4205 1914 gi|1256742 R27-2 protein [Trypanosoma cruzi] 41 27 2292 368 2 2 943 gi|21783 LMW glutenin (AA 1-356) [Triticum aestivum] 41 34 942 155 3 4489 2861 gi|42023 member of ATP-dependent transport family, very similar to 40 18 1629 mdr proteins and hemolysin B, export protein [Escherichia coli] 365 2 95 1438 gi|1633572 Herpesvirus saimiri ORF73 homolog [Kaposi's 40 21 1344 sarcoma-associated herpes-like virus] 1 3 2979 3860 gnl|PID|d101908 hypothetical protein [Synechocystis sp.] 39 26 882 1 5 3814 4647 gnl|PID|d101961 hypothetical protein [Synechocystis sp.] 39 19 834 26 6 14035 10724 gi|142439 ATP-dependent nuclease [Bacillus subtilis] 38 20 3312 47 1 3 4916 gi|632549 NF-180 [Petromyzon marinus] 36 23 4914

TABLE 3 S. pneumoniae Putative coding regions of novel proteins not similar to known proteins Contig ORF Start Stop ID ID (nt) (nt) 1 4 3428 3009 1 6 4611 4964 3 2 818 994 3 3 1182 1574 3 7 5382 6497 3 25 25046 25396 3 26 25625 26317 6 2 1519 1689 6 14 12875 12618 6 15 13215 12841 6 18 15977 15390 7 12 9955 9419 7 13 10161 9910 8 6 3915 4280 9 9 6024 5704 10 8 6909 6298 10 9 7136 6888 10 11 7968 7672 12 1 1140 4 12 3 1779 1456 14 2 1913 1434 16 1 1 243 16 5 5675 3087 17 1 324 34 17 3 1451 1050 17 9 4890 4465 20 14 14544 15893 21 3 3359 2589 21 5 4802 4482 22 21 17099 17362 22 25 19467 19982 22 33 25540 25764 22 35 26388 26218 22 36 26382 27572 23 7 6655 6032 23 8 7132 6653 24 1 36 518 25 5 3009 2641 27 4 4819 4223 27 5 4789 4956 28 5 3017 1797 28 8 4272 3850 28 10 5028 4597 28 11 5746 5072 29 7 5596 4919 29 8 5039 5518 29 9 5595 8207 30 9 6511 6263 31 6 2664 2344 32 5 5203 5538 33 8 5327 4668 34 10 8024 7740 34 12 9360 8641 34 13 9667 9377 34 18 13104 11902 35 11 9688 8588 35 12 11073 9670 36 2 334 1041 36 12 11120 10893 36 13 10993 11388 36 15 12172 14595 38 7 4269 4577 38 8 4480 5001 38 10 5517 5711 38 17 10732 11376 40 3 1728 3143 43 1 172 5 43 7 8884 8732 43 8 9568 9071 44 4 4831 6831 45 3 3204 3665 46 4 3875 3468 46 7 6074 7081 48 5 3196 3582 48 8 4579 4229 48 11 9323 8922 48 16 13042 12494 48 20 16342 15764 48 24 17971 18351 48 30 21979 21776 49 1 209 3 50 4 3307 2672 51 5 3239 3598 52 11 12146 12883 54 7 5588 5187 54 8 6013 5459 54 9 6004 6210 54 16 17685 17506 55 9 10515 10123 55 12 11947 12141 56 3 935 1387 56 4 1496 1939 57 3 1624 2130 57 4 2100 2501 58 6 7541 7335 59 1 2 430 59 4 2416 2736 59 5 2734 3063 59 8 4743 5549 59 9 5459 5929 60 6 5741 6451 61 3 2395 1772 61 5 3316 3176 64 1 2722 2 66 2 1180 3147 66 8 9082 9495 67 3 1343 1182 69 2 1165 980 70 5 4059 3922 70 6 4215 4057 70 9 5268 5504 71 15 20351 21901 71 16 21859 22338 71 19 26204 27556 72 9 8458 8081 73 4 3815 4216 73 6 4214 4582 73 7 4369 4773 73 10 7183 6428 73 15 9462 9668 76 1 524 195 76 2 867 535 76 11 8602 9210 80 6 7924 8109 81 1 244 2 81 10 6631 8931 83 4 1872 1150 83 17 16810 16460 84 3 4464 2929 86 2 2147 1092 86 4 3606 2875 86 19 16767 17114 87 5 5326 5000 87 7 6459 6001 87 9 7224 7006 87 18 17930 17670 87 19 18275 17928 88 2 1619 1840 88 4 2711 2878 88 9 6252 6016 89 3 2634 1621 89 9 7371 6868 90 2 899 2395 90 3 1143 952 91 3 2959 3141 91 4 3170 3691 91 6 4253 4573 93 1 391 2 93 6 2648 2379 93 8 4533 3712 96 1 3 182 96 2 904 632 96 3 1407 1147 96 4 1250 1420 97 9 7043 6753 99 15 18522 18692 99 17 19717 19541 100 2 4094 1980 103 1 48 299 103 6 4924 4373 104 5 6142 6735 105 7 6098 6517 106 1 1 363 106 10 9832 10212 108 1 2 268 111 3 3417 3788 111 4 3809 4606 115 10 10854 10438 116 3 2873 2121 118 2 2274 1357 122 4 2698 2333 122 10 5858 6199 122 12 6301 7416 124 2 346 690 128 4 2544 3368 129 1 689 102 129 2 1011 724 129 8 6454 6056 129 9 6540 6277 129 12 7809 7621 131 3 1433 756 131 10 5972 5673 134 11 11838 11209 135 2 625 1140 136 4 2913 3830 137 2 325 134 139 12 14027 14521 139 13 14840 14532 139 14 15363 14875 140 20 19822 20838 142 1 1 285 146 3 760 479 146 4 1149 778 146 7 3604 2885 146 13 8223 9401 146 14 9399 10676 146 15 10052 9750 147 7 7488 7276 147 9 8913 8647 148 7 5298 4765 149 1 2 1936 149 3 2557 2880 149 9 6258 6070 150 2 1355 579 150 3 2556 1909 153 3 2061 2642 154 3 1953 1741 155 2 2181 1411 156 8 4550 4311 157 1 37 294 159 2 631 780 159 4 1384 1722 159 7 3271 4017 161 2 1332 1018 165 3 5535 4945 166 6 5406 4972 167 9 6075 6395 169 5 2828 3205 170 7 6485 6243 170 8 6964 6362 170 9 7303 6962 170 11 8790 7906 171 9 7150 7476 172 5 2298 1948 173 4 2913 2677 175 2 659 835 175 3 893 1789 176 2 1487 546 176 3 2200 1466 177 9 4686 4925 177 10 4923 5177 177 11 5111 5347 177 13 7396 8703 178 6 3452 3724 181 5 1853 2473 182 2 2112 1102 182 3 2617 2006 183 2 2126 2320 185 5 4683 4219 185 6 4846 4634 187 4 2940 3557 188 4 3686 4363 188 5 4183 4821 188 6 5882 6493 189 5 3143 2844 189 9 5956 5564 191 1 618 4 191 11 10357 10001 192 3 2861 2268 192 4 3081 2878 192 7 6800 5331 193 3 997 839 194 4 2315 2127 195 5 6249 4543 195 6 6620 6231 196 2 1553 1849 197 1 1 861 198 9 6844 6644 200 5 5329 5769 200 6 5993 6595 204 5 3914 3276 205 2 447 1709 209 4 2038 2460 209 5 2458 2682 210 10 7370 8230 210 13 9029 10441 210 14 10439 10705 214 5 2581 2330 214 9 5065 5277 214 11 5996 5754 217 2 541 194 218 2 914 1432 218 3 1430 1972 218 6 3639 3821 219 1 458 39 220 1 869 600 223 4 2617 1964 227 1 1 510 234 4 1539 1312 234 6 2116 1838 235 1 52 312 235 2 310 687 238 1 660 64 246 1 1 270 248 1 3 362 248 2 443 1222 254 3 2789 792 258 2 1179 1616 260 3 1770 2123 263 1 653 177 263 4 2244 1900 263 5 3569 2973 266 1 1 342 266 2 177 1022 270 2 1124 1681 272 1 857 186 275 2 1684 2295 278 1 2 406 282 1 714 391 282 4 1463 1134 287 2 1119 826 288 1 540 4 289 1 684 4 291 5 1589 1858 293 2 2539 2925 294 1 21 608 296 2 494 700 296 3 670 843 302 1 261 530 309 3 559 350 310 2 249 1889 316 2 2087 1818 317 2 1048 584 318 2 313 777 319 3 477 133 327 2 912 607 331 1 1 549 333 1 2 535 333 2 465 82 333 3 127 342 341 1 1 705 345 2 895 701 346 2 750 199 349 1 1 198 350 2 81 413 355 1 44 973 358 2 636 448 360 2 948 628 364 2 1639 1265 378 1 345 1004 379 2 683 510 381 1 109 693 385 1 150 4 385 2 269 30 

1. An isolated protein-encoding nucleic acid fragment of the Streptococcus pneumoniae genome, wherein said fragment consists of the nucleotide sequence of any one of the fragments of SEQ ID NOS:1-391 depicted in Tables 2 and 3, or a degenerate variant thereof.
 2. A vector comprising any one of the fragments of the Streptococcus pneumoniae genome of claim
 1. 3. An organism which has been altered to contain any one of the fragments of the Streptococcus pneumoniae genome of claim
 1. 4. An isolated polypeptide encoded by any of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and depicted in Table 2 and 3 or by a degenerate variant of said fragments.
 5. An isolated polynucleotide molecule encoding any one of the polypeptides of claim
 4. 6. An antibody which selectively binds to any one of the polypeptides of claim
 4. 7. A method for producing a polypeptide in a host cell comprising the steps of: a) incubating a host containing a heterologous nucleic acid molecule whose nucleotide sequence consists of any one of the fragments of the Streptococcus pneumoniae genome of SEQ ID NOS:1-391 and depicted in Tables 2 and 3, under conditions where said heterologous nucleic acid molecule is expressed to produce said protein, and b) isolating said protein. 